The DOI matches its Crossref record; 236 of the 236 references it cites were found in a registry or an index; 1 of the 356 sources its claims cite were checked for support.
Pathogenesis of Insulin Resistance in Skeletal Muscle
Open accessAbstract
Insulin resistance in skeletal muscle is manifested by decreased insulin-stimulated glucose uptake and results from impaired insulin signaling and multiple post-receptor intracellular defects including impaired glucose transport, glucose phosphorylation, and reduced glucose oxidation and glycogen synthesis. Insulin resistance is a core defect in type 2 diabetes, it is also associated with obesity and the metabolic syndrome. Dysregulation of fatty acid metabolism plays a pivotal role in the pathogenesis of insulin resistance in skeletal muscle. Recent studies have reported a mitochondrial defect in oxidative phosphorylation in skeletal muscle in variety of insulin resistant states. In this review, we summarize the cellular and molecular defects that contribute to the development of insulin resistance in skeletal muscle.
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153 Not checked yet · 54 Own interpretation · 10 No basis given · 1 Partly supported · 1 Own method · 1 Own result · accuracy not yet measured
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In the paper
“Lastly, experimental induction of insulin resistance in skeletal muscle, by a physiological increase in plasma FFA concentration in lean healthy insulin-sensitive individuals, is associated with a decrease in oxidative phosphorylation flux in skeletal muscle [110].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.2. Increased Fat Supply or Impaired Mitochondrial Function in Insulin Resistance?
What the sources say
- Partly supportedcites [110] Brehm A Krssak M Schmid AI Nowotny P Waldhäusl W Roden M Increased lipid availability impairs insulin-stimulated ATP synthesis in human skeletal muscle Diabetes 2006 55 1 136 140 16380486 sourceExperimental — accuracy not yet measured
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In the paper
“we recently have demonstrated that a physiologic increase in FACoA concentration inhibits mitochondrial ATP synthesis in vitro in mitochondria isolated from skeletal muscle of NGT healthy lean subjects [132]”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.4. Inherited or Acquired Mitochondrial Defect
What the sources say
- Not checked yetcites [132] Abdul-Ghani MA Muller F Liu Y Deleterious effect of elevated fatty acid metabolites concentration on skeletal muscle mitochondrial ATP synthesis Diabetes 2007 56 supplement 1
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In the paper
“Using the gold standard euglycemic hyperinsulinemic clamp technique to quantify insulin-stimulated glucose uptake, they demonstrated that both lean and obese T2DM subjects have marked decrease (>50%) in whole body glucose disposal during the insulin clamp.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle
What the sources say
- Not checked yetcites [1] DeFronzo RA Pathogenesis of type 2 diabetes: metabolic and molecular implications for identifying diabetes genes Diabetes Reviews 1997 5 3 177 269
- Not checked yetcites [2] DeFronzo RA The triumvirate: β-cell, muscle, liver. A collusion responsible for NIDDM Diabetes 1988 37 6 667 687 3289989 source
- Not checked yetcites [3] DeFronzo RA Pathogenesis of type 2 diabetes mellitus Medical Clinics of North America 2004 88 4 787 835 15308380 source
- Not checked yetcites [4] Defronzo RA From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus Diabetes 2009 58 4 773 795 19336687 PMC2661582 source
- Not checked yetcites [5] DeFronzo RA Gunnarsson R Bjorkman O Olsson M Wahren J Effects of insulin on peripheral and splanchnic glucose metabolism in noninsulin-dependent (type II) diabetes mellitus The Journal of Clinical Investigation 1985 76 1 149 155 3894418 PMC423730 source
- Not checked yetcites [21] Groop LC Bonadonna RC DelPrato S Glucose and free fatty acid metabolism in non-insulin-dependent diabetes mellitus. Evidence for multiple sites of insulin resistance The Journal of Clinical Investigation 1989 84 1 205 213 2661589 PMC303971 source
- Not checked yetcites [27] DeFronzo RA Deibert D Hendler R Felig P Soman V Insulin sensitivity and insulin binding to monocytes in maturity-onset diabetes The Journal of Clinical Investigation 1979 63 5 939 946 376552 PMC372035 source
- Not checked yetcites [28] DeFronzo RA Soman V Sherwin RS Hendler R Felig P Insulin binding to monocytes and insulin action in human obesity, starvation, and refeeding The Journal of Clinical Investigation 1978 62 1 204 213 350903 PMC371755 source
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In the paper
“In addition, the onset of insulin action in skeletal muscle in T2DM subjects is markedly delayed (Figure 2).”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle
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In the paper
“suggest that this mitochondrial defect contributes to the increased intramyocellar fat content.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 1. Introduction
What the sources say
- Not checked yetcites [16] Roden M Muscle triglycerides and mitochondrial function: possible mechanisms for the development of type 2 diabetes International Journal of Obesity 2005 29 supplement 2 S111 S115 16385762 source
- Not checked yetcites [17] Morino K Petersen KF Shulman GI Molecular mechanisms of insulin resistance in humans and their potential links with mitochondrial dysfunction Diabetes 2006 55 supplement 2 S9 S15 17130651 PMC2995546 source
- Not checked yetcites [18] Abdul-Ghani MA DeFronzo RA Mitochondrial dysfunction, insulin resistance, and type 2 diabetes mellitus Current Diabetes Reports 2008 8 3 173 178 18625112 source
- Not checked yetcites [19] Højlund K Mogensen M Sahlin K Beck-Nielsen H Mitochondrial dysfunction in type 2 diabetes and obesity Endocrinology and Metabolism Clinics of North America 2008 37 3 713 731 18775360 source
- Not checked yetcites [20] Lowell BB Shulman GI Mitochondrial dysfunction and type 2 diabetes Science 2005 307 5708 384 387 15662004 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“Thus, under postprandial conditions, for example, mixed meal, muscle energy metabolism switches from predominant oxidizion of fat during the fasting state, to predominant oxidizion of glucose [22].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 2. Normal Skeletal Muscle Metabolism
What the sources say
- Not checked yetcites [22] Blaak EE Metabolic fluxes in skeletal muscle in relation to obesity and insulin resistance Best Practice and Research: Clinical Endocrinology and Metabolism 2005 19 3 391 403 16150382 source
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In the paper
“Following a meal, approximately one third of ingested glucose is taken up by the liver and the rest by peripheral tissues, primarily skeletal muscle via an insulin dependent mechanism [1–4].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 1. Introduction
What the sources say
- Not checked yetcites [1] DeFronzo RA Pathogenesis of type 2 diabetes: metabolic and molecular implications for identifying diabetes genes Diabetes Reviews 1997 5 3 177 269
- Not checked yetcites [2] DeFronzo RA The triumvirate: β-cell, muscle, liver. A collusion responsible for NIDDM Diabetes 1988 37 6 667 687 3289989 source
- Not checked yetcites [3] DeFronzo RA Pathogenesis of type 2 diabetes mellitus Medical Clinics of North America 2004 88 4 787 835 15308380 source
- Not checked yetcites [4] Defronzo RA From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus Diabetes 2009 58 4 773 795 19336687 PMC2661582 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“In contrast, during the last hour of the insulin clamp study, the rate of glucose uptake is reduced by ~50% in lean T2DM subjects (Figure 2).”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“an increased intramyocellar fat content and fatty acid metabolites have been shown to play a pivotal role in the development of insulin resistance in skeletal muscle [11–15].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 1. Introduction
What the sources say
- Not checked yetcites [11] Lettner A Roden M Ectopic fat and insulin resistance Current Diabetes Reports 2008 8 3 185 191 18625114 source
- Not checked yetcites [12] McGarry JD Banting lecture 2001: dysregulation of fatty acid metabolism in the etiology of type 2 diabetes Diabetes 2002 51 1 7 18 11756317 source
- Not checked yetcites [13] Petersen KF Shulman GI Etiology of insulin resistance American Journal of Medicine 2006 119 5, supplement 1 10S 16S PMC2995525 16563942 source
- Not checked yetcites [14] Bays H Mandarino L DeFronzo RA Role of the adipocyte, free fatty acids, and ectopic fat in pathogenesis of type 2 diabetes mellitus: peroxisomal proliferator-activated receptor agonists provide a rational therapeutic approach Journal of Clinical Endocrinology and Metabolism 2004 89 2 463 478 14764748 source
- Not checked yetcites [15] Krssak M Roden M The role of lipid accumulation in liver and muscle for insulin resistance and type 2 diabetes mellitus in humans Reviews in Endocrine and Metabolic Disorders 2004 5 2 127 134 15041788 source
boosteddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Insulin resistance in skeletal muscle also can develop independent of family history of T2DM.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle
What the sources say
- Not checked yetcites [33] Kahn SE Hull RL Utzschneider KM Mechanisms linking obesity to insulin resistance and type 2 diabetes Nature 2006 444 7121 840 846 213 17167471 source
- Not checked yetcites [34] Bogardus C Lillioja S Mott D Reaven GR Kashiwagi A Foley JE Relationship between obesity and maximal insulin-stimulated glucose uptake in vivo and in vitro in Pima Indians The Journal of Clinical Investigation 1984 73 3 800 805 6368588 PMC425083 source
- Not checked yetcites [35] Ferrannini E Buzzigoli G Bonadonna R Insulin resistance in essential hypertension The New England Journal of Medicine 1987 317 6 350 357 3299096 source
- Not checked yetcites [36] Bressler P Bailey SR Matsuda M DeFronzo RA Insulin resistance and coronary artery disease Diabetologia 1996 39 11 1345 1350 8933003 source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“In lean healthy individuals insulin stimulates glucose uptake into skeletal muscle in a dose-dependent manner, with a half-maximal effect (EC50) at a plasma insulin concentration ~60 μU/mL [21].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle
What the sources say
- Not checked yetcites [21] Groop LC Bonadonna RC DelPrato S Glucose and free fatty acid metabolism in non-insulin-dependent diabetes mellitus. Evidence for multiple sites of insulin resistance The Journal of Clinical Investigation 1989 84 1 205 213 2661589 PMC303971 source
plaindirect- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“Dysregulation of fatty acid metabolism plays a pivotal role in the pathogenesis of insulin resistance in skeletal muscle.”
- Also stated in: § 1. Introduction · boosted
“an increased intramyocellar fat content and fatty acid metabolites have been shown to play a pivotal role in the development of insulin resistance in skeletal muscle [11–15].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > Abstract
What the sources say
- Not checked yetcites [11] Lettner A Roden M Ectopic fat and insulin resistance Current Diabetes Reports 2008 8 3 185 191 18625114 source
- Not checked yetcites [12] McGarry JD Banting lecture 2001: dysregulation of fatty acid metabolism in the etiology of type 2 diabetes Diabetes 2002 51 1 7 18 11756317 source
- Not checked yetcites [13] Petersen KF Shulman GI Etiology of insulin resistance American Journal of Medicine 2006 119 5, supplement 1 10S 16S PMC2995525 16563942 source
- Not checked yetcites [14] Bays H Mandarino L DeFronzo RA Role of the adipocyte, free fatty acids, and ectopic fat in pathogenesis of type 2 diabetes mellitus: peroxisomal proliferator-activated receptor agonists provide a rational therapeutic approach Journal of Clinical Endocrinology and Metabolism 2004 89 2 463 478 14764748 source
- Not checked yetcites [15] Krssak M Roden M The role of lipid accumulation in liver and muscle for insulin resistance and type 2 diabetes mellitus in humans Reviews in Endocrine and Metabolic Disorders 2004 5 2 127 134 15041788 source
boosteddirect- Asserted: passes — The authors put it forward as true.
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- Also stated in: § 1. Introduction · boosted
None of the sources cited for this claim have been checked yet.
In the paper
“Recent studies have reported a mitochondrial defect in oxidative phosphorylation in skeletal muscle in variety of insulin resistant states.”
- Also stated in: § 1. Introduction · plain
“The recent studies have reported the existence of a defect in mitochondrial oxidative phosphorylation in skeletal muscle in insulin resistance states [16–20]”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > Abstract
What the sources say
- Not checked yetcites [16] Roden M Muscle triglycerides and mitochondrial function: possible mechanisms for the development of type 2 diabetes International Journal of Obesity 2005 29 supplement 2 S111 S115 16385762 source
- Not checked yetcites [17] Morino K Petersen KF Shulman GI Molecular mechanisms of insulin resistance in humans and their potential links with mitochondrial dysfunction Diabetes 2006 55 supplement 2 S9 S15 17130651 PMC2995546 source
- Not checked yetcites [18] Abdul-Ghani MA DeFronzo RA Mitochondrial dysfunction, insulin resistance, and type 2 diabetes mellitus Current Diabetes Reports 2008 8 3 173 178 18625112 source
- Not checked yetcites [19] Højlund K Mogensen M Sahlin K Beck-Nielsen H Mitochondrial dysfunction in type 2 diabetes and obesity Endocrinology and Metabolism Clinics of North America 2008 37 3 713 731 18775360 source
- Not checked yetcites [20] Lowell BB Shulman GI Mitochondrial dysfunction and type 2 diabetes Science 2005 307 5708 384 387 15662004 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Also stated in: § 1. Introduction · plain
In the paper
“Under euglycemic conditions studies, using the insulin clamp in combination with femoral artery and vein catheterization [5] has shown that approximately 80% of total body glucose uptake occurs in skeletal muscle.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle
What the sources say
- Not checked yetcites [5] DeFronzo RA Gunnarsson R Bjorkman O Olsson M Wahren J Effects of insulin on peripheral and splanchnic glucose metabolism in noninsulin-dependent (type II) diabetes mellitus The Journal of Clinical Investigation 1985 76 1 149 155 3894418 PMC423730 source
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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In the paper
“Insulin resistance in skeletal muscle is manifested long before the hyperglycemia becomes evident [2].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle
What the sources say
- Not checked yetcites [2] DeFronzo RA The triumvirate: β-cell, muscle, liver. A collusion responsible for NIDDM Diabetes 1988 37 6 667 687 3289989 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Skeletal muscle is the major site for disposal of ingested glucose in lean healthy normal glucose tolerance (NGT) individuals [1–4].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 1. Introduction
What the sources say
- Not checked yetcites [1] DeFronzo RA Pathogenesis of type 2 diabetes: metabolic and molecular implications for identifying diabetes genes Diabetes Reviews 1997 5 3 177 269
- Not checked yetcites [2] DeFronzo RA The triumvirate: β-cell, muscle, liver. A collusion responsible for NIDDM Diabetes 1988 37 6 667 687 3289989 source
- Not checked yetcites [3] DeFronzo RA Pathogenesis of type 2 diabetes mellitus Medical Clinics of North America 2004 88 4 787 835 15308380 source
- Not checked yetcites [4] Defronzo RA From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus Diabetes 2009 58 4 773 795 19336687 PMC2661582 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Thus, lean healthy offspring of diabetic parents have a significant decrease in insulin-stimulated total body and muscle glucose disposal which is of a similar magnitude to that observed in their diabetic parents [30–32].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle
What the sources say
- Not checked yetcites [30] Kashyap SR Belfort R Berria R Discordant effects of a chronic physiological increase in plasma FFA on insulin signaling in healthy subjects with or without a family history of type 2 diabetes American Journal of Physiology 2004 287 3 E537 E546 15126243 source
- Not checked yetcites [31] Danadian K Balasekaran G Lewy V Meza MP Robertson R Arslanian SA Insulin sensitivity in African-American children with and without family history of type 2 diabetes Diabetes Care 1999 22 8 1325 1329 10480778 source
- Not checked yetcites [32] Petersen KF Dufour S Befroy D Garcia R Shulman GI Impaired mitochondrial activity in the insulin-resistant offspring of patients with type 2 diabetes The New England Journal of Medicine 2004 350 7 664 671 14960743 PMC2995502 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“In insulin resistance states, such as T2DM and obesity, insulin-stimulated glucose disposal in skeletal muscle is markedly impaired [1–6].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 1. Introduction
What the sources say
- Not checked yetcites [1] DeFronzo RA Pathogenesis of type 2 diabetes: metabolic and molecular implications for identifying diabetes genes Diabetes Reviews 1997 5 3 177 269
- Not checked yetcites [2] DeFronzo RA The triumvirate: β-cell, muscle, liver. A collusion responsible for NIDDM Diabetes 1988 37 6 667 687 3289989 source
- Not checked yetcites [3] DeFronzo RA Pathogenesis of type 2 diabetes mellitus Medical Clinics of North America 2004 88 4 787 835 15308380 source
- Not checked yetcites [4] Defronzo RA From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus Diabetes 2009 58 4 773 795 19336687 PMC2661582 source
- Not checked yetcites [5] DeFronzo RA Gunnarsson R Bjorkman O Olsson M Wahren J Effects of insulin on peripheral and splanchnic glucose metabolism in noninsulin-dependent (type II) diabetes mellitus The Journal of Clinical Investigation 1985 76 1 149 155 3894418 PMC423730 source
- Not checked yetcites [6] Mitrakou A Kelley D Veneman T Contribution of abnormal muscle and liver glucose metabolism to postprandial hyperglycemia in NIDDM Diabetes 1990 39 11 1381 1390 2121568 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Insulin resistance in skeletal muscle also can develop secondary to pharmacological therapy, for example, glucocorticoids [44], anti-HIV therapy [45], and beta blockers [46].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle
What the sources say
- Not checked yetcites [44] Pagano G Cavallo-Perin P Cassader M An in vivo and in vitro study of the mechanism of prednisone-induced insulin resistance in healthy subjects The Journal of Clinical Investigation 1983 72 5 1814 1820 6355186 PMC370470 source
- Not checked yetcites [45] Hruz PW HIV protease inhibitors and insulin resistance: lessons from in-vitro, rodent and healthy human volunteer models Current Opinion in HIV and AIDS 2008 3 6 660 665 19373039 PMC2680222 source
- Not checked yetcites [46] Jacob S Rett K Wicklmayr M Agrawal B Augustin HJ Dietze G-J Differential effect of chronic treatment with two beta-blocking agents on insulin sensitivity: the carvedilol-metoprolol study Journal of Hypertension 1996 14 4 489 494 8761899
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The inhibition of insulin signaling and induction of skeletal muscle insulin resistance caused by elevation in the plasma FFA concentration is dose dependent [65].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.1. Relationship between Obesity and Insulin Resistance in Skeletal Muscle
What the sources say
- Not checked yetcites [65] Belfort R Mandarino L Kashyap S Dose-response effect of elevated plasma free fatty acid on insulin signaling Diabetes 2005 54 6 1640 1648 15919784 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Nondiabetic obese and type 2 diabetic individuals are characterized by day-long elevation in the plasma FFA concentration, which fails to suppress normally after ingestion of a mixed meal or an oral glucose load [60].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.1. Relationship between Obesity and Insulin Resistance in Skeletal Muscle
What the sources say
- Not checked yetcites [60] Reaven GM Hollenbeck C Jeng C-Y Wu MS Chen Y-DI Measurement of plasma glucose, free fatty acid, lactate, and insulin for 24 h in patients with NIDDM Diabetes 1988 37 8 1020 1024 3292322 source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“The noninsulin dependent glucose uptake in skeletal muscle also is decreased in insulin resistant individuals [47].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle
What the sources say
- Not checked yetcites [47] Jani R Molina M Matsuda M Decreased non-insulin-dependent glucose clearance contributes to the rise in fasting plasma glucose in the nondiabetic range Diabetes Care 2008 31 2 311 315 18000182 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“It is well established that chronically elevated plasma FFA levels cause insulin resistance in skeletal muscle [1, 12, 14, 62–65].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.1. Relationship between Obesity and Insulin Resistance in Skeletal Muscle
What the sources say
- Not checked yetcites [1] DeFronzo RA Pathogenesis of type 2 diabetes: metabolic and molecular implications for identifying diabetes genes Diabetes Reviews 1997 5 3 177 269
- Not checked yetcites [12] McGarry JD Banting lecture 2001: dysregulation of fatty acid metabolism in the etiology of type 2 diabetes Diabetes 2002 51 1 7 18 11756317 source
- Not checked yetcites [14] Bays H Mandarino L DeFronzo RA Role of the adipocyte, free fatty acids, and ectopic fat in pathogenesis of type 2 diabetes mellitus: peroxisomal proliferator-activated receptor agonists provide a rational therapeutic approach Journal of Clinical Endocrinology and Metabolism 2004 89 2 463 478 14764748 source
- Not checked yetcites [62] Griffin ME Marcucci MJ Cline GW Free fatty acid-induced insulin resistance is associated with activation of protein kinase C θ and alterations in the insulin signaling cascade Diabetes 2000 48 6 1270 1274 10342815 source
- Not checked yetcites [63] Dresner A Laurent D Marcucci M Effects of free fatty acids on glucose transport and IRS-1-associated phosphatidylinositol 3-kinase activity The Journal of Clinical Investigation 1999 103 2 253 259 9916137 PMC407880 source
- Not checked yetcites [64] Yu C Chen Y Cline GW Mechanism by which fatty acids inhibit insulin activation of insulin receptor substrate-1 (IRS-1)-associated phosphatidylinositol 3-kinase activity in muscle The Journal of Biological Chemistry 2002 277 52 50230 50236 12006582 source
- Not checked yetcites [65] Belfort R Mandarino L Kashyap S Dose-response effect of elevated plasma free fatty acid on insulin signaling Diabetes 2005 54 6 1640 1648 15919784 source
boosteddirect- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Collectively, these studies demonstrate a causal role of obesity per se in the development of skeletal muscle insulin resistance.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.1. Relationship between Obesity and Insulin Resistance in Skeletal Muscle
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In the paper
“and the severity of muscle insulin resistance is related to the increase in BMI [34].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.1. Relationship between Obesity and Insulin Resistance in Skeletal Muscle
What the sources say
- Not checked yetcites [34] Bogardus C Lillioja S Mott D Reaven GR Kashiwagi A Foley JE Relationship between obesity and maximal insulin-stimulated glucose uptake in vivo and in vitro in Pima Indians The Journal of Clinical Investigation 1984 73 3 800 805 6368588 PMC425083 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“Considerable data implicate a causative role for elevated plasma FFA level in insulin resistance in skeletal muscle.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.1. Relationship between Obesity and Insulin Resistance in Skeletal Muscle
What the sources say
- Not checked yetcites [12] McGarry JD Banting lecture 2001: dysregulation of fatty acid metabolism in the etiology of type 2 diabetes Diabetes 2002 51 1 7 18 11756317 source
- Not checked yetcites [14] Bays H Mandarino L DeFronzo RA Role of the adipocyte, free fatty acids, and ectopic fat in pathogenesis of type 2 diabetes mellitus: peroxisomal proliferator-activated receptor agonists provide a rational therapeutic approach Journal of Clinical Endocrinology and Metabolism 2004 89 2 463 478 14764748 source
- Not checked yetcites [57] Reaven GM Role of insulin resistance in human disease Diabetes 1988 37 12 1595 1607 3056758 source
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“Elevated plasma FFA levels correlate strongly with reduced insulin-stimulated glucose disposal in skeletal muscle [61].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.1. Relationship between Obesity and Insulin Resistance in Skeletal Muscle
What the sources say
- Not checked yetcites [61] Perseghin G Ghosh S Gerow K Shulman GI Metabolic defects in lean nondiabetic offspring of NIDDM parents: a cross-sectional study Diabetes 1997 46 6 1001 1009 9166672 source
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In the paper
“Studies in experimental animals and in man have demonstrated that the increase in body weight is accompanied with an increase in skeletal muscle insulin resistance [48–52].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.1. Relationship between Obesity and Insulin Resistance in Skeletal Muscle
What the sources say
- Not checked yetcites [48] DeFronzo RA Insulin secretion, insulin resistance, and obesity International Journal of Obesity 1982 6 supplement 1 73 82 6749725
- Not checked yetcites [49] Lemay A Turcot L Déchêne F Dodin S Forest JC Hyperinsulinemia in nonobese women reporting a moderate weight gain at the beginning of menopause: a useful early measure of susceptibility to insulin resistance Menopause 2010 17 2 321 325 19745772 source
- Not checked yetcites [50] Wedick NM Snijder MB Dekker JM Prospective investigation of metabolic characteristics in relation to weight gain in older adults: the hoorn study Obesity 2009 17 8 1609 1614 19197256 source
- Not checked yetcites [51] Erdmann J Kallabis B Oppel U Sypchenko O Wagenpfeil S Schusdziarra V Development of hyperinsulinemia and insulin resistance during the early stage of weight gain American Journal of Physiology 2008 294 3 E568 E575 18171910 source
- Not checked yetcites [52] Schrauwen P High-fat diet, muscular lipotoxicity and insulin resistance Proceedings of the Nutrition Society 2007 66 1 33 41 17343770 source
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In the paper
“The mechanism via which obesity causes insulin resistance in skeletal muscle is related to the accumulation of fat in the myocytes.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.1. Relationship between Obesity and Insulin Resistance in Skeletal Muscle
What the sources say
- Not checked yetcites [53] Pan DA Lillioja S Kriketos AD Skeletal muscle triglyceride levels are inversely related to insulin action Diabetes 1997 46 6 983 988 9166669 source
- Not checked yetcites [54] Phillips DIW Caddy S Ilic V Intramuscular triglyceride and muscle insulin sensitivity: evidence for a relationship in nondiabetic subjects Metabolism 1996 45 8 947 950 8769349 source
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In the paper
“The important role of elevated plasma FFA in the pathogenesis of insulin resistance is now well established [12, 14, 57].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.1. Relationship between Obesity and Insulin Resistance in Skeletal Muscle
What the sources say
- Not checked yetcites [12] McGarry JD Banting lecture 2001: dysregulation of fatty acid metabolism in the etiology of type 2 diabetes Diabetes 2002 51 1 7 18 11756317 source
- Not checked yetcites [14] Bays H Mandarino L DeFronzo RA Role of the adipocyte, free fatty acids, and ectopic fat in pathogenesis of type 2 diabetes mellitus: peroxisomal proliferator-activated receptor agonists provide a rational therapeutic approach Journal of Clinical Endocrinology and Metabolism 2004 89 2 463 478 14764748 source
- Not checked yetcites [57] Reaven GM Role of insulin resistance in human disease Diabetes 1988 37 12 1595 1607 3056758 source
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In the paper
“The majority of insulin resistant individuals, both diabetic and nondiabetics, are overweight or obese [58]”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.1. Relationship between Obesity and Insulin Resistance in Skeletal Muscle
What the sources say
- Not checked yetcites [58] Mokdad AH Ford ES Bowman BA Diabetes trends in the U.S.: 1990–1998 Diabetes Care 2000 23 9 1278 1283 10977060 source
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In the paper
“Obese NGT subjects display marked skeletal muscle insulin resistance compared to lean age and sex matched individuals [33, 34]”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.1. Relationship between Obesity and Insulin Resistance in Skeletal Muscle
What the sources say
- Not checked yetcites [33] Kahn SE Hull RL Utzschneider KM Mechanisms linking obesity to insulin resistance and type 2 diabetes Nature 2006 444 7121 840 846 213 17167471 source
- Not checked yetcites [34] Bogardus C Lillioja S Mott D Reaven GR Kashiwagi A Foley JE Relationship between obesity and maximal insulin-stimulated glucose uptake in vivo and in vitro in Pima Indians The Journal of Clinical Investigation 1984 73 3 800 805 6368588 PMC425083 source
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In the paper
“Conversely, weight loss in obese NGT individuals improves/reverses insulin resistance in skeletal muscle [43].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.1. Relationship between Obesity and Insulin Resistance in Skeletal Muscle
What the sources say
- Not checked yetcites [43] Van Cromphaut SJ Vanhorebeek I Van den Berghe G Glucose metabolism and insulin resistance in sepsis Current Pharmaceutical Design 2008 14 19 1887 1899 18691100 source
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In the paper
“(iii) the increase in insulin resistance caused by elevating the plasma FFA concentration in insulin sensitive individuals is associated with an increase in the intramyocellar fat content [74];”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.1. Relationship between Obesity and Insulin Resistance in Skeletal Muscle
What the sources say
- Not checked yetcites [74] Boden G Lebed B Schatz M Homko C Lemieux S Effects of acute changes of plasma free fatty acids on intramyocellular fat content and insulin resistance in healthy subjects Diabetes 2001 50 7 1612 1617 11423483 source
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In the paper
“However, the transport of LCFA by CD36 into skeletal muscle does not seem to regulate the rate of LCFA oxidation.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.2. Increased Fat Supply or Impaired Mitochondrial Function in Insulin Resistance?
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In the paper
“Lean normal-glucose-tolerant (NGT), insulin-resistant offspring of T2DM parents have a 30–40% decrease in metabolic flux through the tricarboxylic acid cycle [104] and oxidative phosphorylation [31] in skeletal muscle under basal conditions.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.2. Increased Fat Supply or Impaired Mitochondrial Function in Insulin Resistance?
What the sources say
- Not checked yetcites [104] Befroy DE Petersen KF Dufour S Impaired mitochondrial substrate oxidation in muscle of insulin-resistant offspring of type 2 diabetic patients Diabetes 2007 56 5 1376 1381 17287462 PMC2995532 source
- Not checked yetcites [31] Danadian K Balasekaran G Lewy V Meza MP Robertson R Arslanian SA Insulin sensitivity in African-American children with and without family history of type 2 diabetes Diabetes Care 1999 22 8 1325 1329 10480778 source
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In the paper
“Further, insulin has been reported to increase CD36 content in skeletal muscle [99].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.2. Increased Fat Supply or Impaired Mitochondrial Function in Insulin Resistance?
What the sources say
- Not checked yetcites [99] Jain SS Chabowski A Snook LA Additive effects of insulin and muscle contraction on fatty acid transport and fatty acid transporters, FAT/CD36, FABPpm, FATP1, 4 and 6 FEBS Letters 2009 583 13 2294 2300 19527715 source
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In the paper
“Electron microscopic studies have revealed a significant reduction (~40%) in mitochondrial density in skeletal muscle in lean NGT offspring of type 2 diabetic parents, in obese nondiabetic individuals and in T2DM subjects compared to lean insulin-sensitive, age-matched controls [111, 112].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.3. Qualitative or Quantitative Mitochondrial Defect
What the sources say
- Not checked yetcites [111] Morino K Petersen KF Dufour S Reduced mitochondrial density and increased IRS-1 serine phosphorylation in muscle of insulin-resistant offspring of type 2 diabetic parents The Journal of Clinical Investigation 2005 115 12 3587 3593 16284649 PMC1280967 source
- Not checked yetcites [112] Ritov VB Menshikova EV He J Ferrell RE Goodpaster BH Kelley DE Deficiency of subsarcolemmal mitochondria in obesity and type 2 diabetes Diabetes 2005 54 1 8 14 15616005 source
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In the paper
“(i) in insulin resistant individuals, insulin-stimulated glucose disposal correlates more strongly with intramyocellar fat content than with the extramtocellar fat [55, 56];”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.1. Relationship between Obesity and Insulin Resistance in Skeletal Muscle
What the sources say
- Not checked yetcites [55] Perseghin G Scifo P De Cobelli F Intramyocellular triglyceride content is a determinant of in vivo insulin resistance in humans: a 1H-13C nuclear magnetic resonance spectroscopy assessment in offspring of type 2 diabetic parents Diabetes 1999 48 8 1600 1606 10426379 source
- Not checked yetcites [56] Krssak M Falk Petersen K Dresner A Intramyocellular lipid concentrations are correlated with insulin sensitivity in humans: a 1H NMR spectroscopy study Diabetologia 1999 42 1 113 116 10027589 source
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In the paper
“indicating that the mitochondrial defect in oxidative phosphorylation may contribute to the impairment in exercise capacity in insulin-resistant individuals.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.2. Increased Fat Supply or Impaired Mitochondrial Function in Insulin Resistance?
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In the paper
“A similar impairment in resting flux through oxidative phosphorylation also has been reported in subjects with type 2 diabetes [105].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.2. Increased Fat Supply or Impaired Mitochondrial Function in Insulin Resistance?
What the sources say
- Not checked yetcites [105] Szendroedi J Schmid AI Chmelik M Muscle mitochondrial ATP synthesis and glucose transport/phosphorylation in type 2 diabetes PLoS Medicine 2007 4 5, article e154 PMC1858707 17472434 source
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In the paper
“Collectively, these results indicate that, regardless of its etiology, insulin resistance in skeletal muscle is associated with decreased mitochondrial oxidative phosphorylation.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.2. Increased Fat Supply or Impaired Mitochondrial Function in Insulin Resistance?
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In the paper
“Furthermore, unlike lean insulin-sensitive individuals, both diabetic subjects and NGT insulin-resistant offspring of two diabetic parents fail to increase mitochondrial oxidative phosphorylation flux following insulin stimulation despite a significant increase in glucose disposal in skeletal muscle [105, 106].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.2. Increased Fat Supply or Impaired Mitochondrial Function in Insulin Resistance?
What the sources say
- Not checked yetcites [105] Szendroedi J Schmid AI Chmelik M Muscle mitochondrial ATP synthesis and glucose transport/phosphorylation in type 2 diabetes PLoS Medicine 2007 4 5, article e154 PMC1858707 17472434 source
- Not checked yetcites [106] Petersen KF Dufour S Shulman GI Decreased insulin-stimulated ATP synthesis and phosphate transport in muscle of insulin-resistant offspring of type 2 diabetic parents PLoS Medicine 2005 2 9, article e233 PMC1184227 16089501 source
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In the paper
“Much evidence supports the hypothesis that the lipotoxic action of FFA on skeletal muscle insulin sensitivity is due to an increase in intramyocellar fat content:”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.1. Relationship between Obesity and Insulin Resistance in Skeletal Muscle
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In the paper
“All three of these scenarios would result in a reduced in ATP synthesis rate measured in vivo with MRS.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.3. Qualitative or Quantitative Mitochondrial Defect
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In the paper
“(iv) in animals, a high fat diet causes an increase in intramuscular fat content, which correlates closely both with the severity and temporal development of insulin resistance [75, 76];”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.1. Relationship between Obesity and Insulin Resistance in Skeletal Muscle
What the sources say
- Not checked yetcites [75] Storlien LH Jenkins AB Chisholm DJ Pascoe WS Khouri S Kraegen EW Influence of dietary fat composition on development of insulin resistance in rats. Relationship to muscle triglyceride and ω-3 fatty acids in muscle phospholipid Diabetes 1991 40 2 280 289 1991575 source
- Not checked yetcites [76] Pagliassotti MJ Pan D Prach P Koppenhafer T Storlien L Hill JO Tissue oxidative capacity, fuel stores and skeletal muscle fatty acid composition in obesity-prone and obesity-resistant rats Obesity Research 1995 3 5 459 464 8521165 source
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In the paper
“In one study that compared muscle fat oxidation across the leg in obese (BMI = 34 kg/m2) compared to lean (BMI = 23 kg/m2) individuals, the rate of fatty acid oxidation was reduced in the obese group despite similar arterial FFA concentrations [100].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.2. Increased Fat Supply or Impaired Mitochondrial Function in Insulin Resistance?
What the sources say
- Not checked yetcites [100] Kelley DE Goodpaster B Wing RR Simoneau J-A Skeletal muscle fatty acid metabolism in association with insulin resistance, obesity, and weight loss American Journal of Physiology 1999 277 6 E1130 E1141 10600804 source
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In the paper
“Studies in humans, using molecular, biochemical, and MR spectroscopic techniques, have documented a defect in mitochondrial oxidative phosphorylation in a variety of insulin resistance states.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.2. Increased Fat Supply or Impaired Mitochondrial Function in Insulin Resistance?
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In the paper
“These results suggest the presence of impaired muscle fat oxidation independent of fat supply to skeletal muscle.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.2. Increased Fat Supply or Impaired Mitochondrial Function in Insulin Resistance?
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In the paper
“Several studies have reported decreased fat oxidation in skeletal muscle, independent of the plasma FFA concentration [100–102].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.2. Increased Fat Supply or Impaired Mitochondrial Function in Insulin Resistance?
What the sources say
- Not checked yetcites [100] Kelley DE Goodpaster B Wing RR Simoneau J-A Skeletal muscle fatty acid metabolism in association with insulin resistance, obesity, and weight loss American Journal of Physiology 1999 277 6 E1130 E1141 10600804 source
- Not checked yetcites [101] Hulver MW Berggren JR Cortright RN Skeletal muscle lipid metabolism with obesity American Journal of Physiology 2003 284 4 E741 E747 12626325 source
- Not checked yetcites [102] Steinberg GR Parolin ML Heigenhauser GJF Dyck DJ Leptin increases FA oxidation in lean but not obese human skeletal muscle: evidence of peripheral leptin resistance American Journal of Physiology 2002 283 1 E187 E192 12067860 source
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In the paper
“Collectively, these results support a causative role of elevated plasma FFA levels in the pathogenesis of insulin resistance in skeletal muscle and have been referred to as “lipotoxicity” [73].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.1. Relationship between Obesity and Insulin Resistance in Skeletal Muscle
What the sources say
- Not checked yetcites [73] Unger RH Lipotoxicity in the pathogenesis of obesity-dependent NIDDM: genetic and clinical implications Diabetes 1995 44 8 863 870 7621989 source
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In the paper
“Thus, an increae in plasma FFA concentration is an important regulator of FFA supply to skeletal muscle [82].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.2. Increased Fat Supply or Impaired Mitochondrial Function in Insulin Resistance?
What the sources say
- Not checked yetcites [82] Abumrad N Coburn C Ibrahimi A Membrane proteins implicated in long-chain fatty acid uptake by mammalian cells: CD36, FATP and FABPm Biochimica et Biophysica Acta 1999 1441 1 4 13 10526223 source
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In the paper
“In vivo measurement of oxidative phosphorylation with 31P-NMR has demonstrated impaired ATP synthesis in a variety of insulin resistant states.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.2. Increased Fat Supply or Impaired Mitochondrial Function in Insulin Resistance?
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In the paper
“With regard to this, several lines of evidence indicate that the mitochondrial defect associated with insulin resistant is reversible, at least in part:”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.4. Inherited or Acquired Mitochondrial Defect
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In the paper
“If the rate of fat supply exceeds the demand for fat oxidation, the muscle redirects the fat entering the cell toward triglyceride synthesis leading to increased IMCL content.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.5. Mitochondrial Defect in Insulin Resistance: Cause or Effect?
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In the paper
“Furthermore, insulin resistance, caused by physiological elevation in plasma FFA concentration in lean healthy individuals, was not associated with a significant change in mitochondrial density in skeletal muscle [117].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.3. Qualitative or Quantitative Mitochondrial Defect
What the sources say
- Not checked yetcites [117] Chavez-Velazquez A Jani R Abdul-Ghani MA Short-Term Elevation of plasma free fatty acids (FFA) decreases skeletal muscle mitochondrial membrane motential in healthy glucose tolerant subjects Diabetes 2007 56 supplement 1
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In the paper
“The ability to reverse the defect in mitochondrial oxidative function argues against an inherited defect.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.4. Inherited or Acquired Mitochondrial Defect
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In the paper
“a mitochondrial defect similar to that observed in insulin-resistant individuals can be produced in young lean healthy subjects by physiologic elevation of the plasma FFA concentration [110, 131]”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.4. Inherited or Acquired Mitochondrial Defect
What the sources say
- Not checked yetcites [110] Brehm A Krssak M Schmid AI Nowotny P Waldhäusl W Roden M Increased lipid availability impairs insulin-stimulated ATP synthesis in human skeletal muscle Diabetes 2006 55 1 136 140 16380486 source
- Not checked yetcites [131] Chavez AO Kamath S Jani R Effect of short-term free fatty acids elevation on mitochondrial function in skeletal muscle of healthy individuals The Journal of Clinical Endocrinology & Metabolism 2010 95 1 422 429 19864449 PMC2805487 source
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In the paper
“Diabetic subjects have been reported to have a decrease in muscle fiber oxygen consumption measured ex vivo.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.3. Qualitative or Quantitative Mitochondrial Defect
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In the paper
“Mutation of these specific tyrosine residues in IRS-1 severely impairs the ability of insulin to stimulate muscle glycogen synthesis, glucose uptake and oxidation, and other acute metabolic- and growth-promoting effects of insulin [142].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.2. Insulin Receptor Signal Transduction
What the sources say
- Not checked yetcites [142] Chou CK Dull TJ Russell DS Human insulin receptors mutated at the ATP-binding site lack protein tyrosine kinase activity and fail to mediate postreceptor effects of insulin The Journal of Biological Chemistry 1987 262 4 1842 1847 3100537 source
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In the paper
“The cellular events via which insulin initiates its stimulatory effect on glucose metabolism start with binding of the hormone to specific receptors that are present on the muscle cell surface [2, 138–140].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance
What the sources say
- Not checked yetcites [2] DeFronzo RA The triumvirate: β-cell, muscle, liver. A collusion responsible for NIDDM Diabetes 1988 37 6 667 687 3289989 source
- Not checked yetcites [138] Saltiel AR Kahn CR Insulin signalling and the regulation of glucose and lipid metabolism Nature 2001 414 6865 799 806 11742412 source
- Not checked yetcites [139] Pessin JE Saltiel AR Signaling pathways in insulin action: molecular targets of insulin resistance The Journal of Clinical Investigation 2000 106 2 165 169 10903329 PMC314316 source
- Not checked yetcites [140] Whitehead JP Clark SF Ursø B James DE Signalling through the insulin receptor Current Opinion in Cell Biology 2000 12 2 222 228 10712920 source
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In the paper
“In contrast if fat oxidation exceeds the rate of fat supply, all fat entering the muscle will be directed to fat oxidation and no fat will accumulate in the muscle.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.5. Mitochondrial Defect in Insulin Resistance: Cause or Effect?
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In the paper
“in vivo mitochondrial ATP synthesis rate, measured with 31P-NMR strongly and inversely correlates with the fasting plasma FFA concentration [105]”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.4. Inherited or Acquired Mitochondrial Defect
What the sources say
- Not checked yetcites [105] Szendroedi J Schmid AI Chmelik M Muscle mitochondrial ATP synthesis and glucose transport/phosphorylation in type 2 diabetes PLoS Medicine 2007 4 5, article e154 PMC1858707 17472434 source
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In the paper
“Although mitochondrial function was not assessed following weight loss in this latter study, the depletion of intramyocellular fat and normalization of insulin sensitivity suggests a reversible mitochondrial defect in these morbidly obese, insulin-resistant individuals;”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.4. Inherited or Acquired Mitochondrial Defect
What the sources say
- Not checked yetcites [124] Greco AV Mingrone G Giancaterini A Insulin resistance in morbid obesity: reversal with intramyocellular fat depletion Diabetes 2002 51 1 144 151 11756334 source
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In the paper
“The decrease in mitochondrial density in skeletal muscle in insulin-resistant individuals is consistent with decreased expression of PGC-1 gene [113], the master regulator for mitochondrial biogenesis.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.3. Qualitative or Quantitative Mitochondrial Defect
What the sources say
- Not checked yetcites [113] Patti ME Butte AJ Crunkhorn S Coordinated reduction of genes of oxidative metabolism in humans with insulin resistance and diabetes: potential role of PGC1 and NRF1 Proceedings of the National Academy of Sciences of the United States of America 2003 100 14 8466 8471 12832613 PMC166252 source
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In the paper
“the morphological changes which characterize mitochondria in obese insulin-resistant individuals [118] can be reversed following weight loss and increased physical activity [119]”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.4. Inherited or Acquired Mitochondrial Defect
What the sources say
- Not checked yetcites [119] Toledo FGS Watkins S Kelley DE Changes induced by physical activity and weight loss in the morphology of intermyofibrillar mitochondria in obese men and women Journal of Clinical Endocrinology and Metabolism 2006 91 8 3224 3227 16684829 source
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In the paper
“Thus, studies which have assessed mitochondrial copy number in skeletal muscle in insulin-resistant individuals have reported conflicting results [114–116].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.3. Qualitative or Quantitative Mitochondrial Defect
What the sources say
- Not checked yetcites [114] Rolo AP Palmeira CM Diabetes and mitochondrial function: role of hyperglycemia and oxidative stress Toxicology and Applied Pharmacology 2006 212 2 167 178 16490224 source
- Not checked yetcites [115] Boushel R Gnaiger E Schjerling P Skovbro M Kraunsøe R Dela F Patients with type 2 diabetes have normal mitochondrial function in skeletal muscle Diabetologia 2007 50 4 790 796 17334651 PMC1820754 source
- Not checked yetcites [116] Asmann YW Stump CS Short KR Skeletal muscle mitochondrial functions, mitochondrial DNA copy numbers, and gene transcript profiles in type 2 diabetic and nondiabetic subjects at equal levels of low or high insulin and euglycemia Diabetes 2006 55 12 3309 3319 17130474 source
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In the paper
“These observations indicate that the mitochondrial defect which accompanies insulin resistance is, at least in part, reversible.”
- Also stated in: § 3.4. Inherited or Acquired Mitochondrial Defect · hedged
“The evidence reviewed above supports the hypothesis that the mitochondrial defect which accompanies insulin resistance is reversible, at least in part, and is likely to be acquired.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.4. Inherited or Acquired Mitochondrial Defect
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In the paper
“suggesting a possible role for elevated plasma FFA/toxic intramyocellar FFA metabolite concentrations in the mitochondrial dysfunction in insulin resistant individuals.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.4. Inherited or Acquired Mitochondrial Defect
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In the paper
“An inherited mitochondrial oxidative defect in the absence (but especially in the presence) of enhanced FFA influx to skeletal muscle would be expected to lead to intramyocellular fat accumulation.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.4. Inherited or Acquired Mitochondrial Defect
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In the paper
“The activation of insulin receptor tyrosine kinase activity is essential for the action of insulin on glucose metabolism.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.1. Insulin Receptor/Insulin Receptor Tyrosine Kinase
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In the paper
“Thus, the IMCL content in skeletal muscle reflects the dynamic balance between the demand for fat oxidation and fat supply to the muscle.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.5. Mitochondrial Defect in Insulin Resistance: Cause or Effect?
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In the paper
“it indicates that elevated plasma FFA/intramyocellular metabolite concentration can cause an acquired mitochondrial defect in oxidative phosphorylation.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.4. Inherited or Acquired Mitochondrial Defect
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In the paper
“The phosphorylated tyrosine residues of IRS-1 mediate an association with the 85-kDa regulatory subunit of phosphatidylinositol 3-kinase (PI3K), leading to activation of the enzyme [138–140, 143, 144].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.2. Insulin Receptor Signal Transduction
What the sources say
- Not checked yetcites [138] Saltiel AR Kahn CR Insulin signalling and the regulation of glucose and lipid metabolism Nature 2001 414 6865 799 806 11742412 source
- Not checked yetcites [139] Pessin JE Saltiel AR Signaling pathways in insulin action: molecular targets of insulin resistance The Journal of Clinical Investigation 2000 106 2 165 169 10903329 PMC314316 source
- Not checked yetcites [140] Whitehead JP Clark SF Ursø B James DE Signalling through the insulin receptor Current Opinion in Cell Biology 2000 12 2 222 228 10712920 source
- Not checked yetcites [143] Virkamäki A Ueki K Kahn CR Protein-protein interaction in insulin signaling and the molecular mechanisms of insulin resistance The Journal of Clinical Investigation 1999 103 7 931 943 10194465 PMC408269 source
- Not checked yetcites [144] Sun XJ Miralpeix M Myers MG Jr. Expression and function of IRS-1 in insulin signal transmission Journal of Biological Chemistry 1992 267 31 22662 22672 1385403 source
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In the paper
“the insulin resistance associated with aging in lean subjects with negative family history of diabetes is associated with a decrease in mitochondrial function [109]”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.4. Inherited or Acquired Mitochondrial Defect
What the sources say
- Not checked yetcites [109] Petersen KF Befroy D Dufour S Mitochondrial dysfunction in the elderly: possible role in insulin resistance Science 2003 300 5622 1140 1142 12750520 PMC3004429 source
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In the paper
“prevention of the IRS-1 serine phosphorylation by mutating key serine residues in the IRS-1 prevents the development of insulin resistance in skeletal muscle caused by high-fat feeding [169].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.5. Insulin-Signaling (IRS-1 and PI3K) Defects (Figure 5)
What the sources say
- Not checked yetcites [169] Morino K Neschen S Bilz S Muscle-pecific IRS-1 ser → ala transgenic mice are protected from fat-induced insulin resistance in skeletal muscle Diabetes 2008 57 10 2644 2651 18633112 PMC2551673 source
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In the paper
“In summary, increased serine phosphorylation of IRS-1 is believed to impair its tyrosine phosphorylation by the insulin receptor and interrupt the insulin signalin cascade, leading to the development of insulin resistance in skeletal muscle.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.5. Insulin-Signaling (IRS-1 and PI3K) Defects (Figure 5)
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In the paper
“Under anabolic conditions, insulin augments glycogen synthesis by simultaneously activating glycogen synthase and inhibiting glycogen phosphorylase [148, 149].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.2. Insulin Receptor Signal Transduction
What the sources say
- Not checked yetcites [148] Dent P Lavoinne A Nakielny S Caudwell FB Watt P Cohen P The molecular mechanism by which insulin stimulates glycogen synthesis in mammalian skeletal muscle Nature 1990 348 6299 302 308 2123524 source
- Not checked yetcites [149] Newgard CB Brady MJ O’Doherty RM Saltiel AR Organizing glucose disposal: emerging roles of the glycogen targeting subunits of protein phosphatase-1 Diabetes 2000 49 12 1967 1977 11117996 source
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In the paper
“This excludes a structural gene abnormality in the insulin receptor as a common cause of insulin resistance in skeletal muscle.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.3. Insulin Receptor Signal Transduction Defects in Insulin Resistance
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In the paper
“Because insulin receptor tyrosine kinase activity assays are performed in vitro, the results of these assays could provide misleading information with regard to insulin receptor function in vivo.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.4. Insulin Receptor Tyrosine Kinase Activity
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“when insulin-stimulated insulin receptor tyrosine phosphorylation was examined in normal-glucose-tolerant insulin-resistant individuals (offspring of two diabetic parents) at high risk for developing type 2 diabetes, a normal increase in tyrosine phosphorylation of the insulin receptor was observed [164].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.4. Insulin Receptor Tyrosine Kinase Activity
What the sources say
- Not checked yetcites [164] Pratipanawatr W Pratipanawatr T Cusi K Skeletal muscle insulin resistance in normoglycemic subjects with a strong family history of type 2 diabetes is associated with decreased insulin-stimulated insulin receptor substrate-1 tyrosine phosphorylation Diabetes 2001 50 7–12 2572 2578 11679436
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In the paper
“In general, serine phosphorylation of IRS-1 negates its ability to undergo tyrosine phosphorylation.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.5. Insulin-Signaling (IRS-1 and PI3K) Defects (Figure 5)
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In the paper
“The insulin receptor gene, however, has been sequenced in a large number of type 2 diabetic patients from diverse ethnic populations and, with very rare exceptions, physiologically significant mutations in the insulin receptor gene have not been observed [159, 160].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.3. Insulin Receptor Signal Transduction Defects in Insulin Resistance
What the sources say
- Not checked yetcites [159] Moller DE Yokota A Flier JS Normal insulin-receptor cDNA sequence in Pima Indians with NIDDM Diabetes 1989 38 11 1496 1500 2620783 source
- Not checked yetcites [160] Kusari J Verma US Buse JB Henry RR Olefsky JM Analysis of the gene sequences of the insulin receptor and the insulin-sensitive glucose transporter (GLUT-4) in patients with common-type non-insulin-dependent diabetes mellitus The Journal of Clinical Investigation 1991 88 4 1323 1330 1918382 PMC295602 source
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In the paper
“insulin binding to solubilized receptors obtained from skeletal muscle and liver has been shown to be normal in obese and lean diabetic individuals [152, 153, 155].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.3. Insulin Receptor Signal Transduction Defects in Insulin Resistance
What the sources say
- Not checked yetcites [152] Caro JF Sinha MK Raju SM Insulin receptor kinase in human skeletal muscle from obese subjects with and without noninsulin dependent diabetes The Journal of Clinical Investigation 1987 79 5 1330 1337 3033021 PMC424378 source
- Not checked yetcites [153] Caro JF Ittoop O Pories WJ Studies on the mechanism of insulin resistance in the liver from humans with noninsulin-dependent diabetes. Insulin action and binding in isolated hepatocytes, insulin receptor structure, and kinase activity The Journal of Clinical Investigation 1986 78 1 249 258 3522628 PMC329556 source
- Not checked yetcites [155] Klein HH Vestergaard H Kotzke G Pedersen O Elevation of serum insulin concentration during euglycemic hyperinsulinemic clamp studies leads to similar activation of insulin receptor kinase in skeletal muscle of subjects with and without NIDDM Diabetes 1995 44 11 1310 1317 7589829 source
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In the paper
“Rodent and human studies have suggested increased serine phosphorylation of IRS-1 in insulin resistant states [111, 171–173].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.5. Insulin-Signaling (IRS-1 and PI3K) Defects (Figure 5)
What the sources say
- Not checked yetcites [111] Morino K Petersen KF Dufour S Reduced mitochondrial density and increased IRS-1 serine phosphorylation in muscle of insulin-resistant offspring of type 2 diabetic parents The Journal of Clinical Investigation 2005 115 12 3587 3593 16284649 PMC1280967 source
- Not checked yetcites [171] Dresner A Laurent D Marcucci M Effects of free fatty acids on glucose transport and IRS-1-associated phosphatidylinositol 3-kinase activity The Journal of Clinical Investigation 1999 103 2 253 259 9916137 PMC407880 source
- Not checked yetcites [172] Khan WA Blobe GC Hannun YA Arachidonic acid and free fatty acids as second messengers and the role of protein kinase C Cellular Signalling 1995 7 3 171 184 7662506 source
- Not checked yetcites [173] Yu C Chen Y Cline GW Mechanism by which fatty acids inhibit insulin activation of insulin receptor substrate-1 (IRS-1)-associated phosphatidylinositol 3-kinase activity in muscle The Journal of Biological Chemistry 2002 277 52 50230 50236 12006582 source
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In the paper
“Increased stress kinase activity also has been implicated in contribute to the serine phosphorylation of IRS-1 and subsequent impairment tyrosine phosphorylation [177, 178].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.5. Insulin-Signaling (IRS-1 and PI3K) Defects (Figure 5)
What the sources say
- Not checked yetcites [177] Tanti J-F Jager J Cellular mechanisms of insulin resistance: role of stress-regulated serine kinases and insulin receptor substrates (IRS) serine phosphorylation Current Opinion in Pharmacology 2009 9 6 753 762 19683471 source
- Not checked yetcites [178] Sell H Eckel J Dietze-Schroeder D Pathways leading to muscle insulin resistance—the muscle-fat connection Archives of Physiology and Biochemistry 2006 112 2 105 113 16931452 source
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In the paper
“These findings are consistent with the concept that impaired insulin receptor tyrosine kinase activity in type 2 diabetic patients is acquired secondary to hyperglycemia or some other metabolic disturbance.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.4. Insulin Receptor Tyrosine Kinase Activity
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In the paper
“In insulin-resistant obese nondiabetic subjects, in the NGT insulin resistant offspring of two diabetic parents, and in type 2 diabetic subjects, a substantial decrease in insulin receptor tyrosine phosphorylation has been demonstrated.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.4. Insulin Receptor Tyrosine Kinase Activity
What the sources say
- Not checked yetcites [7] Cusi K Maezono K Osman A Insulin resistance differentially affects the PI 3-kinase- and MAP kinase-mediated signaling in human muscle The Journal of Clinical Investigation 2000 105 3 311 320 10675357 PMC377440 source
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In the paper
“increased intramyocellar levels of fat metabolites, for example, FACoA and DAG, which are strong activators of protein kinase C, have been demonstrated following lipid infusion [176].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.5. Insulin-Signaling (IRS-1 and PI3K) Defects (Figure 5)
What the sources say
- Not checked yetcites [176] Lam TK Yoshii H Haber CA Free fatty acid-induced hepatic insulin resistance: a potential role for protein kinase C-delta Am J Physiol Endocrinol Metab 2002 283 4 E682 91 12217885 source
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In the paper
“The nature of the defect in IRS-1 that impairs its ability to activate PI3-Kinase does not seem to include a structural defect in IRS-1.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.5. Insulin-Signaling (IRS-1 and PI3K) Defects (Figure 5)
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In the paper
“The decrease in insulin-stimulated association of the p85 regulatory subunit of PI3K with IRS-1 is closely correlated with the reduction in insulin-stimulated muscle glycogen synthase activity and in vivo insulin-stimulated glucose disposal [7].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.5. Insulin-Signaling (IRS-1 and PI3K) Defects (Figure 5)
What the sources say
- Not checked yetcites [7] Cusi K Maezono K Osman A Insulin resistance differentially affects the PI 3-kinase- and MAP kinase-mediated signaling in human muscle The Journal of Clinical Investigation 2000 105 3 311 320 10675357 PMC377440 source
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In the paper
“Activation of PI3K by phosphorylated IRS-1 leads to activation of protein kinase B/Akt which is a central intermediate for many of the metabolic and growth actions of insulin.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.2. Insulin Receptor Signal Transduction
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In the paper
“Most [1, 7, 152, 153, 156, 161] but not all [155] investigators have found a reduction in tyrosine kinase activity that cannot be explained by alterations in insulin receptor number or insulin receptor binding affinity.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.4. Insulin Receptor Tyrosine Kinase Activity
What the sources say
- Not checked yetcites [1] DeFronzo RA Pathogenesis of type 2 diabetes: metabolic and molecular implications for identifying diabetes genes Diabetes Reviews 1997 5 3 177 269
- Not checked yetcites [7] Cusi K Maezono K Osman A Insulin resistance differentially affects the PI 3-kinase- and MAP kinase-mediated signaling in human muscle The Journal of Clinical Investigation 2000 105 3 311 320 10675357 PMC377440 source
- Not checked yetcites [152] Caro JF Sinha MK Raju SM Insulin receptor kinase in human skeletal muscle from obese subjects with and without noninsulin dependent diabetes The Journal of Clinical Investigation 1987 79 5 1330 1337 3033021 PMC424378 source
- Not checked yetcites [153] Caro JF Ittoop O Pories WJ Studies on the mechanism of insulin resistance in the liver from humans with noninsulin-dependent diabetes. Insulin action and binding in isolated hepatocytes, insulin receptor structure, and kinase activity The Journal of Clinical Investigation 1986 78 1 249 258 3522628 PMC329556 source
- Not checked yetcites [156] Kashiwagi A Verso MA Andrews J In vitro insulin resistance of human adipocytes isolated from subjects with noninsulin-dependent diabetes mellitus The Journal of Clinical Investigation 1983 72 4 1246 1254 6355180 PMC370408 source
- Not checked yetcites [161] Nolan JJ Freidenberg G Henry R Reichart D Olefsky JM Role of human skeletal muscle insulin receptor kinase in the in vivo insulin resistance of noninsulin-dependent diabetes mellitus and obesity Journal of Clinical Endocrinology and Metabolism 1994 78 2 471 477 8106637 source
- Not checked yetcites [155] Klein HH Vestergaard H Kotzke G Pedersen O Elevation of serum insulin concentration during euglycemic hyperinsulinemic clamp studies leads to similar activation of insulin receptor kinase in skeletal muscle of subjects with and without NIDDM Diabetes 1995 44 11 1310 1317 7589829 source
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In the paper
“Obese, IGT, and diabetic subjects have severe impairment in insulin-stimulated glycogen synthase that accounts for the majority of the defect in insulin-mediated whole-body glucose disposal [1, 2, 21, 195, 206–218].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.8. Glycogen Synthesis
What the sources say
- Not checked yetcites [1] DeFronzo RA Pathogenesis of type 2 diabetes: metabolic and molecular implications for identifying diabetes genes Diabetes Reviews 1997 5 3 177 269
- Not checked yetcites [2] DeFronzo RA The triumvirate: β-cell, muscle, liver. A collusion responsible for NIDDM Diabetes 1988 37 6 667 687 3289989 source
- Not checked yetcites [21] Groop LC Bonadonna RC DelPrato S Glucose and free fatty acid metabolism in non-insulin-dependent diabetes mellitus. Evidence for multiple sites of insulin resistance The Journal of Clinical Investigation 1989 84 1 205 213 2661589 PMC303971 source
- Not checked yetcites [195] Williams KV Price JC Kelley DE Interactions of impaired glucose transport and phosphorylation in skeletal muscle insulin resistance. A dose-response assessment using positron emission tomography Diabetes 2001 50 9 2069 2079 11522673 source
- Not checked yetcites [206] Gulli G Ferrannini E Stern M Haffner S DeFronzo RA The metabolic profile of NIDDM is fully established in glucose-tolerant offspring of two Mexican-American NIDDM parents Diabetes 1992 41 12 1575 1586 1446799 source
- Not checked yetcites [207] Golay A DeFronzo RA Ferrannini E Oxidative and non-oxidative glucose metabolism in non-obese type 2 (non-insulin-dependent) diabetic patients Diabetologia 1988 31 8 585 591 3065112 source
- Not checked yetcites [208] Lillioja S Mott DM Zawadzki JK Young AA Abbott WG Bogardus C Glucose storage is a major determinant of in vivo ‘insulin resistance’ in subjects with normal glucose tolerance Journal of Clinical Endocrinology and Metabolism 1986 62 5 922 927 3514652 source
- Not checked yetcites [209] Shulman GI Rothman DL Jue T Stein P DeFronzo RA Shulman RG Quantitation of muscle glycogen synthesis in normal subjects and subjects with non-insulin-dependent diabetes by 13C nuclear magnetic resonance spectroscopy The New England Journal of Medicine 1990 322 4 223 228 2403659 source
- Not checked yetcites [210] Rothman DL Magnusson I Cline G Decreased muscle glucose transport/phosphorylation is an early defect in the pathogenesis of non-insulin-dependent diabetes mellitus Proceedings of the National Academy of Sciences of the United States of America 1995 92 4 983 987 7862678 PMC42621 source
- Not checked yetcites [211] Vaag A Henriksen JE Madsbad S Holm N Beck-Nielsen H Insulin secretion, insulin action, and hepatic glucose production in identical twins discordant for non-insulin-dependent diabetes mellitus The Journal of Clinical Investigation 1995 95 2 690 698 7860750 PMC295536 source
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In the paper
“In lean type 2 diabetics, the ability of insulin to augment HK-II activity and mRNA levels are markedly reduced compared with controls [199].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.7. Glucose Phosphorylation
What the sources say
- Not checked yetcites [199] Vogt C Ardehali H Iozzo P Regulation of hexokinase II expression in human skeletal muscle in vivo Metabolism 2000 49 6 814 818 10877213 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Impaired insulin-stimulated glycogen synthesis is a characteristic finding in all insulin-resistant states.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.8. Glycogen Synthesis
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In the paper
“Insulin activates glycogen synthase by stimulating a cascade of phosphorylation-dephosphorylation reactions which ultimately lead to the inhibition of glycogen synthase kinase and activation of PP1 (also called glycogen synthase phosphatase).”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.8. Glycogen Synthesis
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In the paper
“Because of methodologic differences, the results of the triple-tracer technique [192, 193] and magnetic resonance imaging [194] studies cannot be reconciled at present.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.7. Glucose Phosphorylation
What the sources say
- Not checked yetcites [192] Bonadonna RC Del Prato S Saccomani MP Transmembrane glucose transport in skeletal muscle of patients with non-insulin-dependent diabetes The Journal of Clinical Investigation 1993 92 1 486 494 8326013 PMC293636 source
- Not checked yetcites [193] Bonadonna RC Del Prato S Bonora E Roles of glucose transport and glucose phosphorylation in muscle insulin resistance of NIDDM Diabetes 1996 45 supplement 3 915 925 8666143 source
- Not checked yetcites [194] Cline GW Petersen KF Krssak M Impaired glucose transport as a cause of decreased insulin-stimulated muscle glycogen synthesis in type 2 diabetes The New England Journal of Medicine 1999 341 4 240 246 10413736 source
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In the paper
“Intact stimulation of the MAPK pathway by insulin in the presence of insulin resistance in the PI3K pathway may play an important role in the development of atherosclerosis [7].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.5. Insulin-Signaling (IRS-1 and PI3K) Defects (Figure 5)
What the sources say
- Not checked yetcites [7] Cusi K Maezono K Osman A Insulin resistance differentially affects the PI 3-kinase- and MAP kinase-mediated signaling in human muscle The Journal of Clinical Investigation 2000 105 3 311 320 10675357 PMC377440 source
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In the paper
“Thus, an abnormality in the HK-II gene is unlikely to explain the inherited insulin resistance in common variety type 2 diabetes mellitus.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.7. Glucose Phosphorylation
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In the paper
“Glucose phosphorylation and glucose transport are tightly coupled processes [197].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.7. Glucose Phosphorylation
What the sources say
- Not checked yetcites [197] Perriott LM Kono T Whitesell RR Glucose uptake and metabolism by cultured human skeletal muscle cells: rate-limiting steps American Journal of Physiology 2001 281 1 E72 E80 11404224
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Using a novel triple-tracer technique, the in vivo dose-response curve for the action of insulin on glucose transport in forearm skeletal muscle has been examined in type 2 diabetic subjects, and insulin-stimulated inward muscle glucose transport has been shown to be severely impaired [192, 193].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.6. Glucose Transport
What the sources say
- Not checked yetcites [192] Bonadonna RC Del Prato S Saccomani MP Transmembrane glucose transport in skeletal muscle of patients with non-insulin-dependent diabetes The Journal of Clinical Investigation 1993 92 1 486 494 8326013 PMC293636 source
- Not checked yetcites [193] Bonadonna RC Del Prato S Bonora E Roles of glucose transport and glucose phosphorylation in muscle insulin resistance of NIDDM Diabetes 1996 45 supplement 3 915 925 8666143 source
boosteddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“In insulin resistant individuals with T2DM, glucose transport activity is severely impaired [156, 181, 182, 187–189].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.6. Glucose Transport
What the sources say
- Not checked yetcites [156] Kashiwagi A Verso MA Andrews J In vitro insulin resistance of human adipocytes isolated from subjects with noninsulin-dependent diabetes mellitus The Journal of Clinical Investigation 1983 72 4 1246 1254 6355180 PMC370408 source
- Not checked yetcites [181] Shepherd PR Kahn BB Glucose transporters and insulin action: implications for insulin resistance and diabetes mellitus The New England Journal of Medicine 1999 341 4 248 257 10413738 source
- Not checked yetcites [182] Hunter SJ Garvey WT Insulin action and insulin resistance: diseases involving defects in insulin receptors, signal transduction, and the glucose transport effector system American Journal of Medicine 1998 105 4 331 345 9809695 source
- Not checked yetcites [187] Garvey WT Huecksteadt TP Matthaei S Olefsky JM Role of glucose transporters in the cellular insulin resistance of type II non-insulin-dependent diabetes mellitus The Journal of Clinical Investigation 1988 81 5 1528 1536 3366906 PMC442586 source
- Not checked yetcites [188] Zierath JR He L Gumà A Odegaard Wahlström E Klip A Wallberg-Henriksson H Insulin action on glucose transport and plasma membrane GLUT4 content in skeletal muscle from patients with NIDDM Diabetologia 1996 39 10 1180 1189 8897005 source
- Not checked yetcites [189] Krook A Björnholm M Galuska D Characterization of signal transduction and glucose transport in skeletal muscle from type 2 diabetic patients Diabetes 2000 49 2 284 292 10868945 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Insulin resistance in the PI3K signaling pathway contrasts with an intact stimulation of the MAPK pathway by insulin in insulin-resistant type 2 diabetic and obese nondiabetics individuals [7, 165].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.5. Insulin-Signaling (IRS-1 and PI3K) Defects (Figure 5)
What the sources say
- Not checked yetcites [7] Cusi K Maezono K Osman A Insulin resistance differentially affects the PI 3-kinase- and MAP kinase-mediated signaling in human muscle The Journal of Clinical Investigation 2000 105 3 311 320 10675357 PMC377440 source
- Not checked yetcites [165] Krook A Björnholm M Galuska D Characterization of signal transduction and glucose transport in skeletal muscle from type 2 diabetic patients Diabetes 2000 49 2 284 292 10868945 source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“In healthy nondiabetic subjects, a physiologic increase in the plasma insulin concentration for as little as 2 to 4 hours increases muscle HK-II activity, gene transcription, and translation [201].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.7. Glucose Phosphorylation
What the sources say
- Not checked yetcites [201] Mandarino LJ Printz RL Cusi KA Regulation of hexokinase II and glycogen synthase mRNA, protein, and activity in human muscle American Journal of Physiology 1995 269 4 E701 E708 7485484
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Activation of the insulin signal transduction system in skeletal muscle stimulates glucose transport through a mechanism that involves translocation of a large intracellular pool of glucose transporters (associated with low-density microsomes) to the plasma membrane and their subsequent activation after insertion into the cell membrane [181, 182].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.6. Glucose Transport
What the sources say
- Not checked yetcites [181] Shepherd PR Kahn BB Glucose transporters and insulin action: implications for insulin resistance and diabetes mellitus The New England Journal of Medicine 1999 341 4 248 257 10413738 source
- Not checked yetcites [182] Hunter SJ Garvey WT Insulin action and insulin resistance: diseases involving defects in insulin receptors, signal transduction, and the glucose transport effector system American Journal of Medicine 1998 105 4 331 345 9809695 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Glycogen synthase is the key insulin-regulated enzyme that controls the rate of muscle glycogen synthesis [148, 150, 200, 212–214].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.8. Glycogen Synthesis
What the sources say
- Not checked yetcites [148] Dent P Lavoinne A Nakielny S Caudwell FB Watt P Cohen P The molecular mechanism by which insulin stimulates glycogen synthesis in mammalian skeletal muscle Nature 1990 348 6299 302 308 2123524 source
- Not checked yetcites [150] Shepherd PR Nave BT Siddle K Insulin stimulation of glycogen synthesis and glycogen synthase activity is blocked by wortmannin and rapamycin in 3T3-L1 adipocytes: evidence for the involvement of phosphoinositide 3-kinase and p70 ribosomal protein-56 kinase Biochemical Journal 1995 305 1 25 28 7826337 PMC1136424 source
- Not checked yetcites [200] Pendergrass M Koval J Vogt C Insulin-induced hexokinase II expression is reduced in obesity and NIDDM Diabetes 1998 47 3 387 394 9519744 source
- Not checked yetcites [212] Yki-Jarvinen H Mott D Young AA Stone K Bogardus C Regulation of glycogen synthase and phosphorylase activities by glucose and insulin in human skeletal muscle The Journal of Clinical Investigation 1987 80 1 95 100 3110217 PMC442206 source
- Not checked yetcites [213] Frame S Cohen P GSK3 takes centre stage more than 20 years after its discovery Biochemical Journal 2001 359, part 1 1 16 11563964 PMC1222116 source
- Not checked yetcites [214] Cohen P The Croonian Lecture 1998. Identification of a protein kinase cascade of major importance in insulin signal transduction Philosophical Transactions of the Royal Society B 1999 354 1382 485 495 PMC1692513 10212493 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“which would be expected, according to the Randle cycle [234], to inhibit PDH activity and consequently glucose oxidation.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.9. Glycolysis
What the sources say
- Not checked yetcites [234] Randle PJ Garland PB Hales CN Newsholme EA The glucose fatty-acid cycle its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus The Lancet 1963 281 7285 785 789 13990765 source
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In the paper
“Obesity and type 2 diabetes mellitus are associated with accelerated FFA turnover and oxidation [1, 2, 21, 233]”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.9. Glycolysis
What the sources say
- Not checked yetcites [1] DeFronzo RA Pathogenesis of type 2 diabetes: metabolic and molecular implications for identifying diabetes genes Diabetes Reviews 1997 5 3 177 269
- Not checked yetcites [2] DeFronzo RA The triumvirate: β-cell, muscle, liver. A collusion responsible for NIDDM Diabetes 1988 37 6 667 687 3289989 source
- Not checked yetcites [21] Groop LC Bonadonna RC DelPrato S Glucose and free fatty acid metabolism in non-insulin-dependent diabetes mellitus. Evidence for multiple sites of insulin resistance The Journal of Clinical Investigation 1989 84 1 205 213 2661589 PMC303971 source
- Not checked yetcites [233] Groop LC Bonadonna RC Simonson DC Petrides AS Shank M DeFronzo RA Effect of insulin on oxidative and nonoxidative pathways of free fatty acid metabolism in human obesity American Journal of Physiology 1992 263 1 E79 E84 1636701
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“In type 2 diabetic patients, insulin-stimulated PDH activity has been shown to be decreased in human skeletal muscle [231, 232].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.9. Glycolysis
What the sources say
- Not checked yetcites [231] Mandarino LJ Madar Z Kolterman OG Bell JM Olefsky JM Adipocyte glycogen synthase and pyruvate dehydrogenase in obese and type II diabetic subjects American Journal of Physiology 1986 251 4 E489 E496 3094377
- Not checked yetcites [232] Kelley DE Mokan M Mandarino LJ Intracellular defects in glucose metabolism in obese patients with NIDDM Diabetes 1992 41 6 698 706 1587397 source
boosted- Asserted: passes — The authors put it forward as true.
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In the paper
“Most studies have demonstrated that insulin does not increase glycogen synthase mRNA or protein expression in human muscle [201, 220, 221].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.8. Glycogen Synthesis
What the sources say
- Not checked yetcites [201] Mandarino LJ Printz RL Cusi KA Regulation of hexokinase II and glycogen synthase mRNA, protein, and activity in human muscle American Journal of Physiology 1995 269 4 E701 E708 7485484
- Not checked yetcites [220] Pratipanawatr T Cusi K Ngo P Pratipanawatr W Mandarine LJ DeFronzo RA Normalization of plasma glucose concentration by insulin therapy improves insulin-stimulated glycogen synthesis in type 2 diabetes Diabetes 2002 51 2 462 468 11812756 source
- Not checked yetcites [221] Vestergaard H Lund S Larsen FS Bjerrum OJ Pedersen O Glycogen synthase and phosphofructokinase protein and mRNA levels in skeletal muscle from insulin-resistant patients with non-insulin-dependent diabetes mellitus The Journal of Clinical Investigation 1993 91 6 2342 2350 8514849 PMC443291 source
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In the paper
“Therefore, it is likely that the observed defects in glucose oxidation and PDH activity are acquired secondary to increased FFA oxidation and feedback inhibition of PDH by elevated intracellular levels of acetyl-CoA and reduced availability of NAD.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.9. Glycolysis
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- Rests on an assumption: Basal and insulin-stimulated glucose oxidation rates are not reduced in normal glucose-tolerant offspring of two diabetic parents and in first-degree relatives of type 2 diabetic subjects, but are decreased in overtly diabetic subjects.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In insulin resistant individuals with overt hyperglycemia, for example, T2DM, a number of postbinding defects have been demonstrated, including reduced insulin receptor tyrosine kinase activity and altered insulin signal transduction, decreased glucose transport, diminished glucose phosphorylation, and impaired glycogen synthase activity.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 5. Summary
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In the paper
“Because PP1 dephosphorylates glycogen synthase, leading to its activation, a defect in PP1 appears to play an important role in the muscle insulin resistance of type 2 diabetes mellitus.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.8. Glycogen Synthesis
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In the paper
“a defect in the insulin signaling cascade at the level of IRS-1 is likely the primady defect that leads to insulin resistance in skeletal muscle.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 5. Summary
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In the paper
“In insulin-resistant nondiabetic and diabetic Pima Indians, activation of muscle PP1 (glycogen synthase phosphatase) by insulin is severely reduced [219].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.8. Glycogen Synthesis
What the sources say
- Not checked yetcites [219] Nyomba BL Freymond D Raz I Stone K Mott DM Bogardus C Skeletal muscle glycogen synthase activity in subjects with non-insulin-dependent diabetes mellitus after glyburide therapy Metabolism 1990 39 11 1204 1210 2122177 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“this defect is present long before the onset of overt diabetes, that is, in normal glucose-tolerant, insulin-resistant prediabetic subjects, and in individuals with IGT.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 5. Summary
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In the paper
“Thus, neither mutations in the PP1 and ISPK-1 genes nor abnormalities in their translation can explain the impaired enzymatic activities of glycogen synthase and PP1 that have been observed in vivo.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.8. Glycogen Synthesis
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“The major abnormality in glycogen synthase regulation in type 2 diabetes is its lack of dephosphorylation and activation by insulin, as a result of insulin receptor signaling abnormalities.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.8. Glycogen Synthesis
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“the molecular cause of the defect most likely is related to impaired insulin signal transduction.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.8. Glycogen Synthesis
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“From the quantitative standpoint, impaired glycogen synthesis represents the major pathway responsible for the insulin resistance”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 5. Summary
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Similarly, there is no evidence that an alteration in glycogen phosphorylase plays any role in the abnormality in glycogen formation in type 2 diabetes [228].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.8. Glycogen Synthesis
What the sources say
- Not checked yetcites [228] Schalin-Jantti C Harkonen M Groop LC Impaired activation of glycogen synthase in people at increased risk for developing NIDDM Diabetes 1992 41 5 598 604 1568529 source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Through activation of serine/threonine kinases and serine phosphorylate the IRS-1, fatty acid metabolites impair IRS-1 phosphorylation by the insulin receptor and lead to the defect in insulin signaling in insulin resistant individuals.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 5. Summary
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Other defects in the insulin signaling pathway, for example, diminished insulin binding, when present, are modest and secondary to downregulation of the insulin receptor by chronic hyperinsulinemia.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 5. Summary
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“PDH is a key insulin-regulated enzyme with activity in muscle that is acutely stimulated by insulin [231].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.9. Glycolysis
What the sources say
- Not checked yetcites [231] Mandarino LJ Madar Z Kolterman OG Bell JM Olefsky JM Adipocyte glycogen synthase and pyruvate dehydrogenase in obese and type II diabetic subjects American Journal of Physiology 1986 251 4 E489 E496 3094377
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The ability of insulin to stimulate glycogen synthase also is diminished in the normal glucose-tolerant, insulin-resistant relatives of type 2 diabetic individuals [218].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.8. Glycogen Synthesis
What the sources say
- Not checked yetcites [218] Vaag A Henriksen JE Beck-Nielsen H Decreased insulin activation of glycogen synthase in skeletal muscles in young nonobese Caucasian first-degree relatives of patients with non-insulin-dependent diabetes mellitus The Journal of Clinical Investigation 1992 89 3 782 788 1541672 PMC442922 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The glycogen synthase gene has been the subject of intensive investigation, and DNA sequencing has revealed either no mutations or rare nucleotide substitutions that cannot explain the defect in insulin-stimulated glycogen synthase activity [223–225].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.8. Glycogen Synthesis
What the sources say
- Not checked yetcites [223] Majer M Mott DM Mochizuki H Association of the glycogen synthase locus on 19q13 with NIDDM in Pima Indians Diabetologia 1996 39 3 314 321 8721777 source
- Not checked yetcites [224] Orho M Nikula-Ijas P Schalin-Jantti C Permutt MA Groop LC Isolation and characterization of the human muscle glycogen synthase gene Diabetes 1995 44 9 1099 1105 7657035 source
- Not checked yetcites [225] Bjørbæk C Echwald SM Hubricht P Genetic variants in promoters and coding regions of the muscle glycogen synthase and the insulin-responsive GLUT4 genes in NIDDM Diabetes 1994 43 8 976 983 8039605 source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“most evidence indicates that the activity of PFK is normal [216, 221].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.9. Glycolysis
What the sources say
- Not checked yetcites [216] Mandarino LJ Wright KS Verity LS Effects of insulin infusion on human skeletal muscle pyruvate dehydrogenase, phosphofructokinase, and glycogen synthase: evidence for their role in oxidative and nonoxidative glucose metabolism The Journal of Clinical Investigation 1987 80 3 655 663 2957389 PMC442287 source
- Not checked yetcites [221] Vestergaard H Lund S Larsen FS Bjerrum OJ Pedersen O Glycogen synthase and phosphofructokinase protein and mRNA levels in skeletal muscle from insulin-resistant patients with non-insulin-dependent diabetes mellitus The Journal of Clinical Investigation 1993 91 6 2342 2350 8514849 PMC443291 source
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In the paper
“Glycogen synthase exists in an active (dephosphorylated) and an inactive (phosphorylated) form [148–150].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.8. Glycogen Synthesis
What the sources say
- Not checked yetcites [148] Dent P Lavoinne A Nakielny S Caudwell FB Watt P Cohen P The molecular mechanism by which insulin stimulates glycogen synthesis in mammalian skeletal muscle Nature 1990 348 6299 302 308 2123524 source
- Not checked yetcites [149] Newgard CB Brady MJ O’Doherty RM Saltiel AR Organizing glucose disposal: emerging roles of the glycogen targeting subunits of protein phosphatase-1 Diabetes 2000 49 12 1967 1977 11117996 source
- Not checked yetcites [150] Shepherd PR Nave BT Siddle K Insulin stimulation of glycogen synthesis and glycogen synthase activity is blocked by wortmannin and rapamycin in 3T3-L1 adipocytes: evidence for the involvement of phosphoinositide 3-kinase and p70 ribosomal protein-56 kinase Biochemical Journal 1995 305 1 25 28 7826337 PMC1136424 source
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In the paper
“glycogen synthase activity is severely impaired in type 2 diabetic individuals”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.8. Glycogen Synthesis
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“No structural gene abnormalities in the catalytic subunit of PP1 were detected in Pima Indians.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.8. Glycogen Synthesis
What the sources say
- Not checked yetcites [226] Bjørbæk C Vik TA Echwald SM Cloning of a human insulin-stimulated protein kinase (ISPK-1) gene and analysis of coding regions and mRNA levels of the ISPK-1 and the protein phosphatase-1 genes in muscle from NIDDM patients Diabetes 1995 44 1 90 97 7813820 source
- Not checked yetcites [227] Prochazka M Mochizuki H Baier LJ Cohen PTW Bogardus C Molecular and linkage analysis of type-1 protein phosphatase catalytic beta-subunit gene: lack of evidence for its major role in insulin a resistance in Pima Indians Diabetologia 1995 38 4 461 466 7796987 source
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In the paper
“In type 2 diabetic individuals, the glycolytic/glucose oxidative pathway has been shown to be impaired [229].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.9. Glycolysis
What the sources say
- Not checked yetcites [229] Del Prato S Bonadonna RC Bonora E Characterization of cellular defects of insulin action in type 2 (non-insulin-dependent) diabetes mellitus The Journal of Clinical Investigation 1993 91 2 484 494 8432857 PMC287962 source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“the mRNA levels of both genes were normal in skeletal muscle.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.8. Glycogen Synthesis
What the sources say
- Not checked yetcites [226] Bjørbæk C Vik TA Echwald SM Cloning of a human insulin-stimulated protein kinase (ISPK-1) gene and analysis of coding regions and mRNA levels of the ISPK-1 and the protein phosphatase-1 genes in muscle from NIDDM patients Diabetes 1995 44 1 90 97 7813820 source
- Not checked yetcites [227] Prochazka M Mochizuki H Baier LJ Cohen PTW Bogardus C Molecular and linkage analysis of type-1 protein phosphatase catalytic beta-subunit gene: lack of evidence for its major role in insulin a resistance in Pima Indians Diabetologia 1995 38 4 461 466 7796987 source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Increased intramyocellar fat content and fatty acid metabolites, for example, FACoA and DAG, are likely to play a pivotal role in the development of insulin resistance in skeletal muscle.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 5. Summary
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“Insulin resistance in skeletal muscle is manifested by decreased insulin-stimulated glucose uptake and results from impaired insulin signaling and multiple post-receptor intracellular defects including impaired glucose transport, glucose phosphorylation, and reduced glucose oxidation and glycogen synthesis.”
- Also stated in: § 1. Introduction · plain
“The decreased insulin-stimulated glucose uptake is due to impaired insulin signaling and multiple postreceptor intracellular defects including impaired glucose transport and glucose phosphorylation, and reduced glucose oxidation and glycogen synthesis [7–10] (Table 1).”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > Abstract
What the sources say
- Not checked yetcites [7] Cusi K Maezono K Osman A Insulin resistance differentially affects the PI 3-kinase- and MAP kinase-mediated signaling in human muscle The Journal of Clinical Investigation 2000 105 3 311 320 10675357 PMC377440 source
- Not checked yetcites [8] Bajaj M DeFronzo RA Metabolic and molecular basis of insulin resistance Journal of Nuclear Cardiology 2003 10 3 311 323 12794631 source
- Not checked yetcites [9] Bouzakri K Koistinen HA Zierath JR Molecular mechanisms of skeletal muscle insulin resistance in type 2 diabetes Current Diabetes Reviews 2005 1 2 167 174 18220592 source
- Not checked yetcites [10] Karlsson HKR Zierath JR Insulin signaling and glucose transport in insulin resistant human skeletal muscle Cell Biochemistry and Biophysics 2007 48 2-3 103 113 17709880 source
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- Also stated in: § 1. Introduction · plain
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These studies indicate that insulin resistance in skeletal muscle in subjects with T2DM is manefisted, not only by a reduction in the magnitude of insulin action, but also by s delayed onset of insulin action to”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle
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In the paper
“During the postabsorptive state, the plasma insulin concentration is low. Since the plasma insulin concentration is the principal factor that restrains lipolysis in adipocytes [21] and stimulates glucose uptake in skeletal muscle [21], during the fasting state, muscle glucose uptake is low and the plasma FFA concentration is elevated.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 2. Normal Skeletal Muscle Metabolism
What the sources say
- Not checked yetcites [21] Groop LC Bonadonna RC DelPrato S Glucose and free fatty acid metabolism in non-insulin-dependent diabetes mellitus. Evidence for multiple sites of insulin resistance The Journal of Clinical Investigation 1989 84 1 205 213 2661589 PMC303971 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Thus, under fasting conditions, FFA serves as the principal fuel source for energy production in skeletal muscle, while the brain exclusively utilizes glucose.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 2. Normal Skeletal Muscle Metabolism
What the sources say
- Not checked yetcites [21] Groop LC Bonadonna RC DelPrato S Glucose and free fatty acid metabolism in non-insulin-dependent diabetes mellitus. Evidence for multiple sites of insulin resistance The Journal of Clinical Investigation 1989 84 1 205 213 2661589 PMC303971 source
plain- Asserted: passes — The authors put it forward as true.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Thus, the dose response curve relating insulin-stimulated glucose uptake and the plasma insulin concentration shifts to the right with an increase in EC50 (to ~120–140 μU/mL) in subjects with T2DM (Figure 1).”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The postprandial hyperglycemia stimulates insulin secretion from the pancreas and the rise in plasma insulin concentration stimulates glucose uptake in skeletal muscle leading to the disposal of ingested glucose [1–4].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 1. Introduction
What the sources say
- Not checked yetcites [1] DeFronzo RA Pathogenesis of type 2 diabetes: metabolic and molecular implications for identifying diabetes genes Diabetes Reviews 1997 5 3 177 269
- Not checked yetcites [2] DeFronzo RA The triumvirate: β-cell, muscle, liver. A collusion responsible for NIDDM Diabetes 1988 37 6 667 687 3289989 source
- Not checked yetcites [3] DeFronzo RA Pathogenesis of type 2 diabetes mellitus Medical Clinics of North America 2004 88 4 787 835 15308380 source
- Not checked yetcites [4] Defronzo RA From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus Diabetes 2009 58 4 773 795 19336687 PMC2661582 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Following glucose ingestion, the increase in plasma glucose concentration stimulates insulin secretion from the beta cell and the resultant hyperinsulinemia suppresses lipolysis, leading to decline in plasma FFA concentration and subsequent decrease in the rate of lipid oxidation.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 2. Normal Skeletal Muscle Metabolism
What the sources say
- Not checked yetcites [1] DeFronzo RA Pathogenesis of type 2 diabetes: metabolic and molecular implications for identifying diabetes genes Diabetes Reviews 1997 5 3 177 269
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“However, with increasing plasma insulin concentration, glycogen synthase is activitaed by insulin and glycogen synthesise predominate (~70% of glucose disposal) [24].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 2. Normal Skeletal Muscle Metabolism
What the sources say
- Not checked yetcites [24] Thiebaud D Jacot E DeFronzo RA Maeder E Jequier E Felber JP The effect of graded doses of insulin on total glucose uptake, glucose oxidation, and glucose storage in man Diabetes 1982 31 11 957 963 6757014 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Muscle insulin resistance strongly correlates with IMCL, independent of total body fat mass and diabetes status [56], while the correlation between EMCL and insulin ressitance is not significant.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.1. Relationship between Obesity and Insulin Resistance in Skeletal Muscle
What the sources say
- Not checked yetcites [56] Krssak M Falk Petersen K Dresner A Intramyocellular lipid concentrations are correlated with insulin sensitivity in humans: a 1H NMR spectroscopy study Diabetologia 1999 42 1 113 116 10027589 source
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“More recent studies [55, 56] using magnetic resonance spectroscopy have demonstrated that although IMCL fat content contributes only a small fraction (~1%) to the total muscle fat content, it plays a key role in the development of insulin resistance in skeletal muscle compared to EMCL.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.1. Relationship between Obesity and Insulin Resistance in Skeletal Muscle
What the sources say
- Not checked yetcites [55] Perseghin G Scifo P De Cobelli F Intramyocellular triglyceride content is a determinant of in vivo insulin resistance in humans: a 1H-13C nuclear magnetic resonance spectroscopy assessment in offspring of type 2 diabetic parents Diabetes 1999 48 8 1600 1606 10426379 source
- Not checked yetcites [56] Krssak M Falk Petersen K Dresner A Intramyocellular lipid concentrations are correlated with insulin sensitivity in humans: a 1H NMR spectroscopy study Diabetologia 1999 42 1 113 116 10027589 source
boosteddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Insulin resistance in skeletal muscle also has been reported in association with the normal ageing process [37], dyslipidemia (increased plasma triglyceride/decreased HDL cholesterol) [4, 26], and in association with many disease states including polycystic ovary syndrome (PCOs) [38], chronic kidney failure [39], heart failure [40], myotonic dystrophy [41], and lipodystrophy [42].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle
What the sources say
- Not checked yetcites [37] DeFronzo RA Glucose intolerance and aging. Evidence for tissue insensitivity to insulin Diabetes 1979 28 12 1095 1101 510806 source
- Not checked yetcites [4] Defronzo RA From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus Diabetes 2009 58 4 773 795 19336687 PMC2661582 source
- Not checked yetcites [26] Ginsberg H Kimmerling G Olefsky JM Reaven GM Demonstration of insulin resistance in untreated adult onset diabetic subjects with fasting hyperglycemia The Journal of Clinical Investigation 1975 55 3 454 461 1117064 PMC301772 source
- Not checked yetcites [38] Lankarani M Valizadeh N Heshmat R Peimani M Sohrabvand F Evaluation of insulin resistance and metabolic syndrome in patients with polycystic ovary syndrome Gynecological Endocrinology 2009 25 8 504 507 19499403 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Thus, obese NGT subjects without a family history for T2DM [33, 34] and individuals with essential hypertension [35] and ischemic heart disease [36] also have a 35–50% decrease in whole body insulin-mediated glucose disposal (Figure 3).”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle
What the sources say
- Not checked yetcites [33] Kahn SE Hull RL Utzschneider KM Mechanisms linking obesity to insulin resistance and type 2 diabetes Nature 2006 444 7121 840 846 213 17167471 source
- Not checked yetcites [34] Bogardus C Lillioja S Mott D Reaven GR Kashiwagi A Foley JE Relationship between obesity and maximal insulin-stimulated glucose uptake in vivo and in vitro in Pima Indians The Journal of Clinical Investigation 1984 73 3 800 805 6368588 PMC425083 source
- Not checked yetcites [35] Ferrannini E Buzzigoli G Bonadonna R Insulin resistance in essential hypertension The New England Journal of Medicine 1987 317 6 350 357 3299096 source
- Not checked yetcites [36] Bressler P Bailey SR Matsuda M DeFronzo RA Insulin resistance and coronary artery disease Diabetologia 1996 39 11 1345 1350 8933003 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Both acute (4 hours) and chronic (4 days) physiologic elevation of plasma FFA concentration in insulin sensitive individuals impairs insulin signaling and causes insulin resistance in skeletal muscle [28, 62–68].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.1. Relationship between Obesity and Insulin Resistance in Skeletal Muscle
What the sources say
- Not checked yetcites [28] DeFronzo RA Soman V Sherwin RS Hendler R Felig P Insulin binding to monocytes and insulin action in human obesity, starvation, and refeeding The Journal of Clinical Investigation 1978 62 1 204 213 350903 PMC371755 source
- Not checked yetcites [62] Griffin ME Marcucci MJ Cline GW Free fatty acid-induced insulin resistance is associated with activation of protein kinase C θ and alterations in the insulin signaling cascade Diabetes 2000 48 6 1270 1274 10342815 source
- Not checked yetcites [63] Dresner A Laurent D Marcucci M Effects of free fatty acids on glucose transport and IRS-1-associated phosphatidylinositol 3-kinase activity The Journal of Clinical Investigation 1999 103 2 253 259 9916137 PMC407880 source
- Not checked yetcites [64] Yu C Chen Y Cline GW Mechanism by which fatty acids inhibit insulin activation of insulin receptor substrate-1 (IRS-1)-associated phosphatidylinositol 3-kinase activity in muscle The Journal of Biological Chemistry 2002 277 52 50230 50236 12006582 source
- Not checked yetcites [65] Belfort R Mandarino L Kashyap S Dose-response effect of elevated plasma free fatty acid on insulin signaling Diabetes 2005 54 6 1640 1648 15919784 source
- Not checked yetcites [66] Itani SI Ruderman NB Schmieder F Boden G Lipid-induced insulin resistance in human muscle is associated with changes in diacylglycerol, protein kinase C, and IκB-α Diabetes 2002 51 7 2005 2011 12086926 source
- Not checked yetcites [67] Richardson DK Kashyap S Bajaj M Lipid infusion decreases the expression of nuclear encoded mitochondrial genes and increases the expression of extracellular matrix genes in human skeletal muscle The Journal of Biological Chemistry 2005 280 11 10290 10297 15598661 source
- Not checked yetcites [68] Boden G Chen X Effects of fat on glucose uptake and utilization in patients with non-insulin-dependent diabetes The Journal of Clinical Investigation 1995 96 3 1261 1268 7657800 PMC185747 source
plaindirect- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These studies indicate that although insulin resistance in skeletal muscle is a hallmark of T2DM, muscle insulin resistance and the accompanying insulin resistance syndrome are more widely prevalent and the metabolic and clinical consequences of insulin resistance (e.g., increased cardiovascular risk) affect nondiabetic individuals as well.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
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In the paper
“Muscle biopsy studies [53, 54] have demonstrated increased triglyceride content in skeletal muscle of obese NGT subjects compared to lean individuals and an inverse relationship between muscle insulin sensitivity and the intramuscular triglyceride content.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.1. Relationship between Obesity and Insulin Resistance in Skeletal Muscle
What the sources say
- Not checked yetcites [53] Pan DA Lillioja S Kriketos AD Skeletal muscle triglyceride levels are inversely related to insulin action Diabetes 1997 46 6 983 988 9166669 source
- Not checked yetcites [54] Phillips DIW Caddy S Ilic V Intramuscular triglyceride and muscle insulin sensitivity: evidence for a relationship in nondiabetic subjects Metabolism 1996 45 8 947 950 8769349 source
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“In addition, insulin resistance develops in acute severe illnesses such as injury and sepsis, perhaps secondary to the acute inflammatory state that prevails [43].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle
What the sources say
- Not checked yetcites [43] Van Cromphaut SJ Vanhorebeek I Van den Berghe G Glucose metabolism and insulin resistance in sepsis Current Pharmaceutical Design 2008 14 19 1887 1899 18691100 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“In insulin resistant individuals, for example, nondiabetic obese and lean type 2 diabetic subjects, the ability of insulin to inhibit lipolysis and reduce plasma FFA concentration is markedly impaired [21, 59], leading to an increased rate of lipolysis and chronic elevation in the plasma FFA concentration.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.1. Relationship between Obesity and Insulin Resistance in Skeletal Muscle
What the sources say
- Not checked yetcites [21] Groop LC Bonadonna RC DelPrato S Glucose and free fatty acid metabolism in non-insulin-dependent diabetes mellitus. Evidence for multiple sites of insulin resistance The Journal of Clinical Investigation 1989 84 1 205 213 2661589 PMC303971 source
- Not checked yetcites [59] Groop LC Saloranta C Shank M Bonadonna RC Ferrannini E DeFronzo RA The role of free fatty acid metabolism in the pathogenesis of insulin resistance in obesity and noninsulin-dependent diabetes mellitus Journal of Clinical Endocrinology and Metabolism 1991 72 1 96 107 1986032 source
plaindirect- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These observations collectively indicate that muscle triglyceride (which is metabolic inert) is not directly involved in determining insulin sensitivity but rather represents a marker of imbalance between lipid supply and lipid oxidation in skeletal muscle, while increases in intramyocellar FACoA and other lipotoxic metabolites (DAG, ceramide) have a more direct role in the development of skeletal”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.1. Relationship between Obesity and Insulin Resistance in Skeletal Muscle
hedgeddirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The mitochondrial defect in ATP synthesis rate documented in vivo with MRS could be due to a reduction in the number of mitochondria in skeletal muscle with normal function of individual mitochondria, an intrinsic defect in a quantitively normal number of mitochondria, or some combination of the two.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.3. Qualitative or Quantitative Mitochondrial Defect
hedgedconditional- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Indeed, early studies demonstrated the rate of lipolysis was a key determinant of FFA uptake and oxidation in skeletal muscle and documented a linear relationship between the plasma LCFA concentration and their rate of uptake and oxidation in the muscle [85–87].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.2. Increased Fat Supply or Impaired Mitochondrial Function in Insulin Resistance?
What the sources say
- Not checked yetcites [85] Hagenfeldt L Metabolism of free fatty acids and ketone bodies during exercise in normal and diabetic man Diabetes 1979 28 supplement 1 66 70 104895 source
- Not checked yetcites [86] Hagenfeldt L Wahren J Human forearm muscle metabolism during exercise. II. Uptake, release and oxidation of individual FFA and glycerol Scandinavian Journal of Clinical and Laboratory Investigation 1968 21 3 263 276 5708695 source
- Not checked yetcites [87] Havel RJ Ekelund LG Holmgren A Kinetic analysis of the oxidation of palmitate-1-14C in man during prolonged heavy muscular exercise Journal of Lipid Research 1967 8 4 366 373 6033603 source
boosteddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The accumulation of fat inside the muscle fiber could originate from excess supply of FFA to the muscle, a decreased rate of muscle fat oxidation, or some combination of the two.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.2. Increased Fat Supply or Impaired Mitochondrial Function in Insulin Resistance?
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In the paper
“Insulin resistance also is a characteristic feature of the normal aging process and is associated with a decrease in mitochondrial ATP synthesis rate and an increase in intramyocellar fat content [109].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.2. Increased Fat Supply or Impaired Mitochondrial Function in Insulin Resistance?
What the sources say
- Not checked yetcites [109] Petersen KF Befroy D Dufour S Mitochondrial dysfunction in the elderly: possible role in insulin resistance Science 2003 300 5622 1140 1142 12750520 PMC3004429 source
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In the paper
“(vii) weight loss, induced by bariatric surgery, results in a complete normalization of insulin sensitivity despite the presence of continued obesity (BMI reduced from 49 to 39 kg/m2) [79]. The normalization of muscle insulin sensitivity is associated with a reduction of muscle fat content to normal despite a persistent increase in total body fat content [79].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.1. Relationship between Obesity and Insulin Resistance in Skeletal Muscle
What the sources say
- Not checked yetcites [79] Greco AV Mingrone G Giancaterini A Insulin resistance in morbid obesity: reversal with intramyocellular fat depletion Diabetes 2002 51 1 144 151 11756334 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Conversely, reduction of plasma FFA concentration in insulin resistant individuals, for example, type 2 diabetic subjects, augments insulin-stimulated glucose disposal in skeletal muscle [69–72], and the improvement in insulin sensitivity is closely associated with a reduction in intramyocellular FACoA concentration [69].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.1. Relationship between Obesity and Insulin Resistance in Skeletal Muscle
What the sources say
- Not checked yetcites [69] Bajaj M Suraamornkul S Romanelli A Effect of a sustained reduction in plasma free fatty acid concentration on intramuscular long-chain fatty acyl-CoAs and insulin action in type 2 diabetic patients Diabetes 2005 54 11 3148 3153 16249438 source
- Not checked yetcites [70] Bajaj M Suraamornkul S Kashyap S Cusi K Mandarino L DeFronzo RA Sustained reduction in plasma free fatty acid concentration improves insulin action without altering plasma adipocytokine levels in subjects with strong family history of type 2 diabetes Journal of Clinical Endocrinology and Metabolism 2004 89 9 4649 4655 15356076 source
- Not checked yetcites [71] Vaag A Skott P Damsbo P Gall M-A Richter EA Beck-Nielsen H Effect of the antilipolytic nicotinic acid analogue acipimox on whole-body and skeletal muscle glucose metabolism in patients with non-insulin-dependent diabetes mellitus The Journal of Clinical Investigation 1991 88 4 1282 1290 1918378 PMC295597 source
- Not checked yetcites [72] Santomauro ATMG Boden G Silva MER Overnight lowering of free fatty acids with acipimox improves insulin resistance and glucose tolerance in obese diabetic and nondiabetic subjects Diabetes 1999 48 9 1836 1841 10480616 source
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In the paper
“An acquired defect potentially could be reversed or prevented, while an inherited defect would be permanent.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.3. Qualitative or Quantitative Mitochondrial Defect
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In the paper
“There is abundant evidence which indicates that CD36 plays an important role in LCFA uptake into skeletal muscle in rodents and human and its concentration and activity are increased following exercise [89–96].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.2. Increased Fat Supply or Impaired Mitochondrial Function in Insulin Resistance?
What the sources say
- Not checked yetcites [89] Gargiulo CE Stunlsatz-Krouper SM Schaffer JE Localization of adipocyte long-chain fatty acyl-CoA synthetase at the plasma membrane Journal of Lipid Research 1999 40 5 881 892 10224157 source
- Not checked yetcites [90] Ibrahimi A Bonen A Blinn WD Muscle-specific overexpression of FAT/CD36 enhances fatty acid oxidation by contracting muscle, reduces plasma triglycerides and fatty acids, and increases plasma glucose and insulin The Journal of Biological Chemistry 1999 274 38 26761 26766 10480880 source
- Not checked yetcites [91] Febbraio M Abumrad NA Hajjar DP A null mutation in murine CD36 reveals an important role in fatty acid and lipoprotein metabolism The Journal of Biological Chemistry 1999 274 27 19055 19062 10383407 source
- Not checked yetcites [92] Luiken JJFP Arumugam Y Dyck DJ Increased rates of fatty acid uptake and plasmalemmal fatty acid transporters in obese Zucker rats The Journal of Biological Chemistry 2001 276 44 40567 40573 11504711 source
- Not checked yetcites [93] Steinberg GR Dyck DJ Calles-Escandon J Chronic leptin administration decreases fatty acid uptake and fatty acid transporters in rat skeletal muscle The Journal of Biological Chemistry 2002 277 11 8854 8860 11729182 source
- Not checked yetcites [94] Cameron-Smith D Burke LM Angus DJ A short-term, high-fat diet up-regulates lipid metabolism and gene expression in human skeletal muscle American Journal of Clinical Nutrition 2003 77 2 313 318 12540388 source
- Not checked yetcites [95] Roepstorff C Helge JW Vistisen B Kiens B Studies of plasma membrane fatty acid-binding protein and other lipid-binding proteins in human skeletal muscle Proceedings of the Nutrition Society 2004 63 2 239 244 15294037 source
- Not checked yetcites [96] Bonen A Parolin ML Steinberg GR Triacylglycerol accumulation in human obesity and type 2 diabetes is associated with increased rates of skeletal muscle fatty acid transport increased sarcolemmal FAT/CD36 FASEB Journal 2004 18 10 1144 1146 15132977 source
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In the paper
“Since the majority of fat oxidation take place in the mitochondria, impaired fat oxidation in insulin resistant individuals suggests the presence of a mitochondrial defect that contributes to the impaired muscle fat oxidation and increased IMCL fat content.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.2. Increased Fat Supply or Impaired Mitochondrial Function in Insulin Resistance?
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In the paper
“During conditions of decreased fat oxidation and increased CD36 levels, muscle uptake of LCFA increased, resulting in increased muscle triglyceride synthesis and increased IMCL content [97, 98].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.2. Increased Fat Supply or Impaired Mitochondrial Function in Insulin Resistance?
What the sources say
- Not checked yetcites [97] Kiens B Roemen THM Van der Vusse GJ Muscular long-chain fatty acid content during graded exercise in humans American Journal of Physiology 1999 276 2 E352 E357 9950796
- Not checked yetcites [98] Roepstorff C Vistisen B Roepstorff K Kiens B Regulation of plasma long-chain fatty acid oxidation in relation to uptake in human skeletal muscle during exercise American Journal of Physiology 2004 287 4 E696 E705 15186996 source
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In the paper
“(ii) the decrease in insulin resistance brought about by reducing the plasma FFA concentration with acipimox in insulin resistant individuals is associated with a reduction in intracellular FACoA content, and the magnitude of decrease in insulin resistance strongly correlates with the decrease in FACoA content [69];”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.1. Relationship between Obesity and Insulin Resistance in Skeletal Muscle
What the sources say
- Not checked yetcites [69] Bajaj M Suraamornkul S Romanelli A Effect of a sustained reduction in plasma free fatty acid concentration on intramuscular long-chain fatty acyl-CoAs and insulin action in type 2 diabetic patients Diabetes 2005 54 11 3148 3153 16249438 source
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In the paper
“(v) in rodents, injection of recombinant adiponectin increases fat oxidation, reduces intamyocellular lipid, and improves insulin sensitivity [77];”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.1. Relationship between Obesity and Insulin Resistance in Skeletal Muscle
What the sources say
- Not checked yetcites [77] Yamauchi T Kamon J Waki H The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity Nature Medicine 2001 7 8 941 946 11479627 source
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In the paper
“Subjects with T2DM also have decreased exercise tolerance and impaired recovery of intracellular phosphocreatinine concentration following exercise [107, 108]”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.2. Increased Fat Supply or Impaired Mitochondrial Function in Insulin Resistance?
What the sources say
- Not checked yetcites [107] Scheuermann-Freestone M Madsen PL Manners D Abnormal cardiac and skeletal muscle energy metabolism in patients with type 2 diabetes Circulation 2003 107 24 3040 3046 12810608 source
- Not checked yetcites [108] Schrauwen-Hinderling VB Kooi ME Hesselink MKC Impaired in vivo mitochondrial function but similar intramyocellular lipid content in patients with type 2 diabetes mellitus and BMI-matched control subjects Diabetologia 2007 50 1 113 120 17093944 source
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In the paper
“More recent studies have reported that under conditions of marked increase in energy demand in the muscle, for example, during exercise, LCFAs uptake initially increases linearly then plateaus [88], suggesting the existence of a facilitated transport mechanism for LCFA into skeletal muscle.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.2. Increased Fat Supply or Impaired Mitochondrial Function in Insulin Resistance?
What the sources say
- Not checked yetcites [88] Kiens B Essen-Gustavsson B Christensen NJ Saltin B Skeletal muscle substrate utilization during submaximal exercise in man: effect of endurance training Journal of Physiology 1993 469 459 478 8271208 PMC1143880 source
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In the paper
“The CD36 content and LCFA transport capacity have been reported to be increased in obese and T2DM individuals and correlate with increased muscle triglyceride content, while fat oxidation is decreased.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.2. Increased Fat Supply or Impaired Mitochondrial Function in Insulin Resistance?
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In the paper
“Collectively, these studies indicate the existence of an intrensic defect in mitochondrial capacity to oxidize fat in obesity and T2DM.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.2. Increased Fat Supply or Impaired Mitochondrial Function in Insulin Resistance?
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In the paper
“(vi) muscle-specific over expression of lipoprotein lipase leads to the accumulation of fat/FACoA in muscle and severe muscle insulin resistance, while the fat content and insulin sensitivity in other tissues, that is, liver, remain unchanged [78];”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.1. Relationship between Obesity and Insulin Resistance in Skeletal Muscle
What the sources say
- Not checked yetcites [78] Kim JK Fillmore JJ Chen Y Tissue-specific overexpression of lipoprotein lipase causes tissue-specific insulin resistance Proceedings of the National Academy of Sciences of the United States of America 2001 98 13 7522 7527 11390966 PMC34701 source
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In the paper
“The mitochondrial defect in oxidative phosphorylation described in vivo with MRS and ex vivo in muscle fibers and isolated mitochondria could contribute to the increase in intramyocellar FFA metabolite levels observed in obesity and T2DM and contribute to the insulin resistance.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.5. Mitochondrial Defect in Insulin Resistance: Cause or Effect?
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In the paper
“one cannot completely exclude the possibility that the mitochondrial defect results secondary to insulin resistance.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.5. Mitochondrial Defect in Insulin Resistance: Cause or Effect?
What the sources say
- Not checked yetcites [110] Brehm A Krssak M Schmid AI Nowotny P Waldhäusl W Roden M Increased lipid availability impairs insulin-stimulated ATP synthesis in human skeletal muscle Diabetes 2006 55 1 136 140 16380486 source
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In the paper
“Thus, normal mitochondrial function in young, insulin-sensitive subjects suggests that the mitochondrial defect and insulin-resistance are acquired as part of the normal ageing process.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.4. Inherited or Acquired Mitochondrial Defect
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In the paper
“An inherited defect in mitochondrial oxidative capacity should be present at or shortly after birth and, most importantly, not be reversable.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.4. Inherited or Acquired Mitochondrial Defect
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Down regulation of electron transport chain activity in mice by knocking down apoptosis inintiating factor (AIF) resulted in enhanced insulin sensitivity and protection the animal from fat-induced insulin resistance [137].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.5. Mitochondrial Defect in Insulin Resistance: Cause or Effect?
What the sources say
- Not checked yetcites [137] Pospisilik JA Knauf C Joza N Targeted deletion of AIF decreases mitochondrial oxidative phosphorylation and protects from obesity and diabetes Cell 2007 131 3 476 491 17981116 source
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In the paper
“(i) modest weight reduction (~10% of body weight), produced by dieting and increased physical activity, reduces insulin resistance and intramyocellular lipid content and these changes are associated with increased fat oxidation in skeletal muscle [123]. Furthermore, the magnitude of increase in fat oxidation following weight loss correlated strongly with the decrease in insulin resistance [123];”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.4. Inherited or Acquired Mitochondrial Defect
What the sources say
- Not checked yetcites [123] Goodpaster BH Katsiaras A Kelley DE Enhanced fat oxidation through physical activity is associated with improvements in insulin sensitivity in obesity Diabetes 2003 52 9 2191 2197 12941756 source
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In the paper
“Down regulation of mitochondrial function in myotubes with oligomycin, which inhibits mitochondrial ATP synthesis, and with ethidium bromide, which impairs mitochondrial DNA replication, caused an increase in intracellular fat content, impaired insulin signaling, and decreased insulin-stimulated glucose uptake [135].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.5. Mitochondrial Defect in Insulin Resistance: Cause or Effect?
What the sources say
- Not checked yetcites [135] Lim JH Lee JI Suh YH Kim W Song JH Jung MH Mitochondrial dysfunction induces aberrant insulin signalling and glucose utilisation in murine C2C12 myotube cells Diabetologia 2006 49 8 1924 1936 16736133 source
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In the paper
“Over expression of the PGC-1 alpha gene in skeletal muscle in mice in vivo enhanced mitochondrial activity, augmented the expression of multiple proteins involved in fat oxidation and glucose transport, and increased by ~35% insulin-stimulated glucose uptake [133].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.5. Mitochondrial Defect in Insulin Resistance: Cause or Effect?
What the sources say
- Not checked yetcites [133] Benton CR Nickerson JG Lally J Modest PGC-1α overexpression in muscle in vivo is sufficient to increase insulin sensitivity and palmitate oxidation in subsarcolemmal, not intermyofibrillar, mitochondria The Journal of Biological Chemistry 2008 283 7 4228 4240 18079123 source
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In the paper
“Biochemical studies have reported a decrease in the activity of a variety of mitochondrial enzymes [122], also supporting an intrinsic functional mitochondrial defect in type 2 diabetic subjects.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.3. Qualitative or Quantitative Mitochondrial Defect
What the sources say
- Not checked yetcites [122] Mogensen M Sahlin K Fernström M Mitochondrial respiration is decreased in skeletal muscle of patients with type 2 diabetes Diabetes 2007 56 6 1592 1599 17351150 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“(ii) marked weight reduction following bariatric surgery in morbidly obese, severely insulin-resistant subjects completely normalized insulin sensitivity, and correction of the insulin resistance was accompanied by depletion of intramyocellar fat content [124].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.4. Inherited or Acquired Mitochondrial Defect
What the sources say
- Not checked yetcites [124] Greco AV Mingrone G Giancaterini A Insulin resistance in morbid obesity: reversal with intramyocellular fat depletion Diabetes 2002 51 1 144 151 11756334 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“An intrinsic mitochondrial defect, with or without a decrease in mitochondrial density, would be expected to result in impaired lipid oxidation, an increase in intramyocellular lipid content, and the development/exacerbation of insulin resistance.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.3. Qualitative or Quantitative Mitochondrial Defect
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In the paper
“In summary it can be concluded that both decreased mitochondrial fat oxidation and increased FFA influx into skeletal muscle take place during insulin resistance state.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.5. Mitochondrial Defect in Insulin Resistance: Cause or Effect?
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In the paper
“Mutagenesis of any of the three major phosphorylation sites (at residues 1158, 1163, and 1162) impairs insulin receptor tyrosine kinase activity, leading to a decrease in the metabolic and growth-promoting effects of insulin [141, 142].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.1. Insulin Receptor/Insulin Receptor Tyrosine Kinase
What the sources say
- Not checked yetcites [141] Ellis L Clauser E Morgan DO Edery M Roth RA Rutter WJ Replacement of insulin receptor tyrosine residues 1162 and 1163 compromises insulin-stimulated kinase activity and uptake of 2-deoxyglucose Cell 1986 45 5 721 732 3518947 source
- Not checked yetcites [142] Chou CK Dull TJ Russell DS Human insulin receptors mutated at the ATP-binding site lack protein tyrosine kinase activity and fail to mediate postreceptor effects of insulin The Journal of Biological Chemistry 1987 262 4 1842 1847 3100537 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Ex vivo measurement of electron transport chain activity (ETC) [112] and mitochondrial ATP synthesis in isolated mitochondria [120, 121] have demonstrated a decrease in ETC activity and ATP synthesis in obese insulin-resistant individuals compared to lean insulin-sensitive subjects.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.3. Qualitative or Quantitative Mitochondrial Defect
What the sources say
- Not checked yetcites [112] Ritov VB Menshikova EV He J Ferrell RE Goodpaster BH Kelley DE Deficiency of subsarcolemmal mitochondria in obesity and type 2 diabetes Diabetes 2005 54 1 8 14 15616005 source
- Not checked yetcites [120] Abdul-Ghani MA Jani R Molina M Chavez A Tripathy D DeFronzo RA Decreased mitochondrial ATP synthesis in obese non-diabetic subjects Diabetes 2008 56 supplement 1
- Not checked yetcites [121] Phielix E Schrauwen-Hinderling VB Mensink M Lower intrinsic ADP-stimulated mitochondrial respiration underlies in vivo mitochondrial dysfunction in muscle of male type 2 diabetic patients Diabetes 2008 57 11 2943 2949 18678616 PMC2570390 source
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“the improvement in insulin sensitivity following exercise is associated with improved muscle oxidative capacity [125, 126] and increases in both mitochondrial density [127] and activity [128–130]”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.4. Inherited or Acquired Mitochondrial Defect
What the sources say
- Not checked yetcites [125] Jubrias SA Esselman PC Price LB Cress ME Conley KE Large energetic adaptations of elderly muscle to resistance and endurance training Journal of Applied Physiology 2001 90 5 1663 1670 11299253 source
- Not checked yetcites [126] Holloszy JO Coyle EF Adaptations of skeletal muscle to endurance exercise and their metabolic consequences Journal of Applied Physiology Respiratory Environmental and Exercise Physiology 1984 56 4 831 838 6373687
- Not checked yetcites [127] Chilibeck PD Syrotuik DG Bell GJ The effect of concurrent endurance and strength training on quantitative estimates of subsarcolemmal and intermyofibrillar mitochondria International Journal of Sports Medicine 2002 23 1 33 39 11774064 source
- Not checked yetcites [128] Østergård T Andersen JL Nyholm B Impact of exercise training on insulin sensitivity, physical fitness, and muscle oxidative capacity in first-degree relatives of type 2 diabetic patients American Journal of Physiology 2006 290 5 E998 E1005 16352678 source
- Not checked yetcites [129] Menshikova EV Ritov VB Toledo FGS Ferrell RE Goodpaster BH Kelley DE Effects of weight loss and physical activity on skeletal muscle mitochondrial function in obesity American Journal of Physiology 2005 288 4 E818 E825 15585590 source
- Not checked yetcites [130] Short KR Vittone JL Bigelow ML Impact of aerobic exercise training on age-related changes in insulin sensitivity and muscle oxidative capacity Diabetes 2003 52 8 1888 1896 12882902 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, when oxygen consumption was related to mitochondrial copy number, both diabetic and nondiabetic subjects had similar rates of muscle oxygen consumption, implying a decrease in mitochondrial density without an intrinsic mitochondrial defect in T2DM subjects.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.3. Qualitative or Quantitative Mitochondrial Defect
hedged- Asserted: passes — The authors put it forward as true.
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In the paper
“Since, in these studies [112, 120], ETC activity and mitochondrial ATP synthesis rate were related to the amount of mitochondrial protein and/or citrate synthase activity, these observations indicate the existence of a basic functional defect in mitochondrial activity in skeletal muscle of obese insulin-resistant individuals [115].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.3. Qualitative or Quantitative Mitochondrial Defect
What the sources say
- Not checked yetcites [112] Ritov VB Menshikova EV He J Ferrell RE Goodpaster BH Kelley DE Deficiency of subsarcolemmal mitochondria in obesity and type 2 diabetes Diabetes 2005 54 1 8 14 15616005 source
- Not checked yetcites [120] Abdul-Ghani MA Jani R Molina M Chavez A Tripathy D DeFronzo RA Decreased mitochondrial ATP synthesis in obese non-diabetic subjects Diabetes 2008 56 supplement 1
- Not checked yetcites [115] Boushel R Gnaiger E Schjerling P Skovbro M Kraunsøe R Dela F Patients with type 2 diabetes have normal mitochondrial function in skeletal muscle Diabetologia 2007 50 4 790 796 17334651 PMC1820754 source
hedgeddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“activation of SIRT1 with resveratrol in mice resulted in increased mitochondrial activity and protected the animals from diet-induced obesity and insulin resistance [134].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.5. Mitochondrial Defect in Insulin Resistance: Cause or Effect?
What the sources say
- Not checked yetcites [134] Lagouge M Argmann C Gerhart-Hines Z Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1α Cell 2006 127 6 1109 1122 17112576 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“EM studies have demonstrated a variety of morphological abnormalities in mitochondria in insulin-resistant individuals [118] and these changes were reversable with weight loss and increased physical activity [119].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.3. Qualitative or Quantitative Mitochondrial Defect
What the sources say
- Not checked yetcites [118] Kelley DE He J Menshikova EV Ritov VB Dysfunction of mitochondria in human skeletal muscle in type 2 diabetes Diabetes 2002 51 10 2944 2950 12351431 source
- Not checked yetcites [119] Toledo FGS Watkins S Kelley DE Changes induced by physical activity and weight loss in the morphology of intermyofibrillar mitochondria in obese men and women Journal of Clinical Endocrinology and Metabolism 2006 91 8 3224 3227 16684829 source
boosteddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“treatment of the muscle cells with azide, an inhibitor of mitochondrial complex IV, increased basal glucose uptake without affecting insulin-stimulated glucose uptake in myotubes [136].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 3. Insulin Resistance in Skeletal Muscle > 3.5. Mitochondrial Defect in Insulin Resistance: Cause or Effect?
What the sources say
- Not checked yetcites [136] Brown AE Elstner M Yeaman SJ Turnbull DM Walker M Does impaired mitochondrial function affect insulin signaling and action in cultured human skeletal muscle cells? American Journal of Physiology 2008 294 1 E97 E102 17957036 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Studies [138, 150] have demonstrated convincingly that inhibitors of PI3K inhibit glycogen synthase activity and abolish glycogen synthesis.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.2. Insulin Receptor Signal Transduction
What the sources say
- Not checked yetcites [138] Saltiel AR Kahn CR Insulin signalling and the regulation of glucose and lipid metabolism Nature 2001 414 6865 799 806 11742412 source
- Not checked yetcites [150] Shepherd PR Nave BT Siddle K Insulin stimulation of glycogen synthesis and glycogen synthase activity is blocked by wortmannin and rapamycin in 3T3-L1 adipocytes: evidence for the involvement of phosphoinositide 3-kinase and p70 ribosomal protein-56 kinase Biochemical Journal 1995 305 1 25 28 7826337 PMC1136424 source
boosteddirect- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, conditions that increase serine phosphorylation of IRS-1 impair tyrosine phosphorylation by the insulin receptor and its activation, thus, leading to an impartment in the insulin signaling cascade.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.5. Insulin-Signaling (IRS-1 and PI3K) Defects (Figure 5)
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Association of the p85 subunit of PI3K with IRS-1 and activation of PI3K also are greatly attenuated in obese nondiabetic and type 2 diabetic subjects compared with lean healthy controls [7, 165, 166].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.5. Insulin-Signaling (IRS-1 and PI3K) Defects (Figure 5)
What the sources say
- Not checked yetcites [7] Cusi K Maezono K Osman A Insulin resistance differentially affects the PI 3-kinase- and MAP kinase-mediated signaling in human muscle The Journal of Clinical Investigation 2000 105 3 311 320 10675357 PMC377440 source
- Not checked yetcites [165] Krook A Björnholm M Galuska D Characterization of signal transduction and glucose transport in skeletal muscle from type 2 diabetic patients Diabetes 2000 49 2 284 292 10868945 source
- Not checked yetcites [166] Kim Y-B Nikoulina SE Ciaraldi TP Henry RR Kahn BB Normal insulin-dependent activation of Akt/protein kinase B, with diminished activation of phosphoinositide 3-kinase, in muscle in type 2 diabetes The Journal of Clinical Investigation 1999 104 6 733 741 10491408 PMC408433 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Increased activity of protein kinase C (PKC-β and δ has been reported in insulin resistant states and can be induced during lipid infusion [174, 175].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.5. Insulin-Signaling (IRS-1 and PI3K) Defects (Figure 5)
What the sources say
- Not checked yetcites [174] Schmitz-Peiffer C Browne CL Oakes ND Alterations in the expression and cellular localization of protein kinase C isozymes ε and θ are associated with insulin resistance in skeletal muscle of the high-fat-fed rat Diabetes 1997 46 2 169 178 9000691 source
- Not checked yetcites [175] Schmitz-Peiffer C Oakes ND Browne CL Kraegen EW Biden TJ Reversal of chronic alterations of skeletal muscle protein kinase C from fat-fed rats by BRL-49653 American Journal of Physiology 1997 273 5 E915 E921 9374677
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“In summary, impaired association of PI3K with IRS-1 and its subsequent activation are characteristic abnormalities in type 2 diabetics, and these defects are correlated closely with in vivo muscle insulin resistance.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.5. Insulin-Signaling (IRS-1 and PI3K) Defects (Figure 5)
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“A common mutation in the IRS-1 gene (Gly-972-Arg) has been associated with type 2 diabetes, insulin resistance, and obesity, but the physiologic significance of this mutation remains to be established [170].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.5. Insulin-Signaling (IRS-1 and PI3K) Defects (Figure 5)
What the sources say
- Not checked yetcites [170] Hitman GA Hawrami K McCarthy MI Insulin receptor substrate-1 gene mutations in NIDDM; implications for the study of polygenic disease Diabetologia 1995 38 4 481 486 7796990 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“The ability of insulin to activate insulin receptor and IRS-1 tyrosine phosphorylation in muscle in obese nondiabetic subjects is modestly reduced; whereas in type 2 diabetics insulin-stimulated insulin receptor and IRS-1 tyrosine phosphorylation are severely impaired [7].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.5. Insulin-Signaling (IRS-1 and PI3K) Defects (Figure 5)
What the sources say
- Not checked yetcites [7] Cusi K Maezono K Osman A Insulin resistance differentially affects the PI 3-kinase- and MAP kinase-mediated signaling in human muscle The Journal of Clinical Investigation 2000 105 3 311 320 10675357 PMC377440 source
plaindirect- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Because nitric oxide synthase also is activated by the IRS-1/PIS-K pathway, impaired insulin signaling leads to reduced nitric oxide generation and endothelial dysfunction, which have implicated in the development of accelerated atherosclerosis in T2DM individuals.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.5. Insulin-Signaling (IRS-1 and PI3K) Defects (Figure 5)
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“a decrease in insulin receptor number cannot be demonstrated in over half of type 2 diabetic subjects, and it has been difficult to demonstrate a correlation between reduced insulin binding and the severity of insulin resistance [156–158].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.3. Insulin Receptor Signal Transduction Defects in Insulin Resistance
What the sources say
- Not checked yetcites [156] Kashiwagi A Verso MA Andrews J In vitro insulin resistance of human adipocytes isolated from subjects with noninsulin-dependent diabetes mellitus The Journal of Clinical Investigation 1983 72 4 1246 1254 6355180 PMC370408 source
- Not checked yetcites [157] Lonnroth P Digirolamo M Krotkiewski M Smith U Insulin binding and responsiveness in fat cells from patients with reduced glucose tolerance and type II diabetes Diabetes 1983 32 8 748 754 6347772 source
- Not checked yetcites [158] Olefsky JM Reaven GM Insulin binding in diabetes. Relationships with plasma insulin levels and insulin sensitivity Diabetes 1977 26 7 680 688 873075 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Inhibition of the MAPK kinase pathway prevents the stimulation of cell growth by insulin but has no effect on the metabolic actions of the hormone [147].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.2. Insulin Receptor Signal Transduction
What the sources say
- Not checked yetcites [147] Lazar DF Wiese RJ Brady MJ Mitogen-activated protein kinase kinase inhibition does not block the stimulation of glucose utilization by insulin The Journal of Biological Chemistry 1995 270 35 20801 20807 7657664 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Inhibitors of PI3K impair glucose transport and block the activation of glycogen synthase and hexokinase- (HK-) II expression [138–146]”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.2. Insulin Receptor Signal Transduction
What the sources say
- Not checked yetcites [138] Saltiel AR Kahn CR Insulin signalling and the regulation of glucose and lipid metabolism Nature 2001 414 6865 799 806 11742412 source
- Not checked yetcites [139] Pessin JE Saltiel AR Signaling pathways in insulin action: molecular targets of insulin resistance The Journal of Clinical Investigation 2000 106 2 165 169 10903329 PMC314316 source
- Not checked yetcites [140] Whitehead JP Clark SF Ursø B James DE Signalling through the insulin receptor Current Opinion in Cell Biology 2000 12 2 222 228 10712920 source
- Not checked yetcites [141] Ellis L Clauser E Morgan DO Edery M Roth RA Rutter WJ Replacement of insulin receptor tyrosine residues 1162 and 1163 compromises insulin-stimulated kinase activity and uptake of 2-deoxyglucose Cell 1986 45 5 721 732 3518947 source
- Not checked yetcites [142] Chou CK Dull TJ Russell DS Human insulin receptors mutated at the ATP-binding site lack protein tyrosine kinase activity and fail to mediate postreceptor effects of insulin The Journal of Biological Chemistry 1987 262 4 1842 1847 3100537 source
- Not checked yetcites [143] Virkamäki A Ueki K Kahn CR Protein-protein interaction in insulin signaling and the molecular mechanisms of insulin resistance The Journal of Clinical Investigation 1999 103 7 931 943 10194465 PMC408269 source
- Not checked yetcites [144] Sun XJ Miralpeix M Myers MG Jr. Expression and function of IRS-1 in insulin signal transmission Journal of Biological Chemistry 1992 267 31 22662 22672 1385403 source
- Not checked yetcites [145] Cross D Alessi D Vandenheed J McDowell H Hundal H Cohen P The inhibition of glycogen synthase kinase-3 by insulin or insulin-like growth factor 1 in the rat skeletal muscle cell line L6 is blocked by wortmannin but not rapamycin Biochemical Journal 1994 267 303 321 PMC1137550 7945242
- Not checked yetcites [146] Osawa H Sutherland C Robey RB Printz RL Granner DK Analysis of the signaling pathway involved in the regulation of hexokinase II gene transcription by insulin The Journal of Biological Chemistry 1996 271 28 16690 16694 8663315 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Early studies have demonstrated a modest 20–30% reduction in insulin binding to monocytes and adipocytes from type 2 diabetic patients, but this has not been a consistent finding [1, 151–154].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.3. Insulin Receptor Signal Transduction Defects in Insulin Resistance
What the sources say
- Not checked yetcites [1] DeFronzo RA Pathogenesis of type 2 diabetes: metabolic and molecular implications for identifying diabetes genes Diabetes Reviews 1997 5 3 177 269
- Not checked yetcites [151] Freidenberg GR Henry RR Klein HH Reichart DR Olefsky JM Decreased kinase activity of insulin receptors from adipocytes of non-insulin-dependent diabetic subjects Journal of Clinical Investigation 1987 79 1 240 250 3540010 PMC424032 source
- Not checked yetcites [152] Caro JF Sinha MK Raju SM Insulin receptor kinase in human skeletal muscle from obese subjects with and without noninsulin dependent diabetes The Journal of Clinical Investigation 1987 79 5 1330 1337 3033021 PMC424378 source
- Not checked yetcites [153] Caro JF Ittoop O Pories WJ Studies on the mechanism of insulin resistance in the liver from humans with noninsulin-dependent diabetes. Insulin action and binding in isolated hepatocytes, insulin receptor structure, and kinase activity The Journal of Clinical Investigation 1986 78 1 249 258 3522628 PMC329556 source
- Not checked yetcites [154] Trischitta V Brunetti A Chiavetta A Benzi L Papa V Vigneri R Defects in insulin-receptor internalization and processing in monocytes of obese subjects and obese NIDDM patients Diabetes 1989 38 12 1579 1584 2684714 source
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Hexokinase isoenzymes (HK-I–IV) catalyze the first committed step of glucose metabolism, the intracellular conversion of free glucose to glucose-6-phosphate (Glu-6-P) [183, 184, 186, 198].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.7. Glucose Phosphorylation
What the sources say
- Not checked yetcites [183] Bell GI Kayano T Buse JB Molecular biology of mammalian glucose transporters Diabetes Care 1990 13 3 198 208 2407475 source
- Not checked yetcites [184] Joost H-G Bell GI Best JD Nomenclature of the GLUT/SLC2A family of sugar/polyol transport facilitators American Journal of Physiology 2002 282 4 E974 E976 11882521
- Not checked yetcites [186] Rogers PA Fisher RA Harris H An electrophoretic study of the distribution and properties of human hexokinases Biochemical Genetics 1975 13 11-12 857 866 1239274 source
- Not checked yetcites [198] Printz RL Ardehali H Koch S Granner DK Human hexokinase II mRNA and gene structure Diabetes 1995 44 3 290 294 7883116 source
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Muscle tissue from lean and obese type 2 diabetic subjects exhibits normal or increased levels of GLUT4 mRNA expression and normal levels of GLUT4 protein, thus demonstrating that transcriptional and translational regulation of GLUT4 is not impaired [190, 191].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.6. Glucose Transport
What the sources say
- Not checked yetcites [190] Pedersen O Bak JF Andersen PH Evidence against altered expression of GLUT1 or GLUT4 in skeletal muscle of patients with obesity for NIDDM Diabetes 1990 39 7 865 870 2354749 source
- Not checked yetcites [191] Eriksson J Koranyi L Bourey R Insulin resistance in type 2 (non-insulin-dependent) diabetic patients and their relatives is not associated with a defect in the expression of the insulin-responsive glucose transporter (GLUT-4) gene in human skeletal muscle Diabetologia 1992 35 2 143 147 1547918 source
boosted- Asserted: passes — The authors put it forward as true.
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In the paper
“Several groups have looked for point mutations in the HK-II gene in individuals with type 2 diabetes, and, although several nucleotide substitutions have been found, none are close to the glucose and ATP binding sites and none have been associated with insulin resistance [203–205].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.7. Glucose Phosphorylation
What the sources say
- Not checked yetcites [203] Lehto M Huang X Davis EM Human hexokinase II gene: exon-intron organization, mutation screening in NIDDM, and its relationship to muscle hexokinase activity Diabetologia 1995 38 12 1466 1474 8786021 source
- Not checked yetcites [204] Laakso M Malkki M Kekalainen P Kuusisto J Deeb SS Polymorphisms of the human hexokinase II gene: lack of association with NIDDM and insulin resistance Diabetologia 1995 38 5 617 622 7489847 source
- Not checked yetcites [205] Echwald SM Bjorbaek C Hansen T Identification of four amino acid substitutions in hexokinase II and studies of relationships to NIDDM, glucose effectiveness, and insulin sensitivity Diabetes 1995 44 3 347 353 7883123 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Large populations of type 2 diabetics have been screened for mutations in the GLUT4 gene [196]. Such mutations are very uncommon and, when detected, have been of questionable physiologic significance.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.6. Glucose Transport
What the sources say
- Not checked yetcites [196] Choi W-H O’Rahilly S Buse JB Molecular scanning of insulin-responsive glucose transporter (GLUT4) gene in NIDDM subjects Diabetes 1991 40 12 1712 1718 1756912 source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Impaired glycogen synthesis also has been documented in the normal-glucose tolerant offspring of two diabetic parents, in the first-degree relatives of type 2 diabetic individuals, and in the normoglycemic twin of a monozygotic twin pair in which the other twin has type 2 diabetes [206, 210, 211].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.8. Glycogen Synthesis
What the sources say
- Not checked yetcites [206] Gulli G Ferrannini E Stern M Haffner S DeFronzo RA The metabolic profile of NIDDM is fully established in glucose-tolerant offspring of two Mexican-American NIDDM parents Diabetes 1992 41 12 1575 1586 1446799 source
- Not checked yetcites [210] Rothman DL Magnusson I Cline G Decreased muscle glucose transport/phosphorylation is an early defect in the pathogenesis of non-insulin-dependent diabetes mellitus Proceedings of the National Academy of Sciences of the United States of America 1995 92 4 983 987 7862678 PMC42621 source
- Not checked yetcites [211] Vaag A Henriksen JE Madsbad S Holm N Beck-Nielsen H Insulin secretion, insulin action, and hepatic glucose production in identical twins discordant for non-insulin-dependent diabetes mellitus The Journal of Clinical Investigation 1995 95 2 690 698 7860750 PMC295536 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These observations indicate that in type 2 diabetic individuals, although both glucose transport and glucose phosphorylation are severely resistant to the action of insulin, impaired glucose phosphorylation (HK-II) appears to be the rate-limiting step for insulin action.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.7. Glucose Phosphorylation
hedgeddirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“In response to physiologic euglycemic hyperinsulinemia of 2 to 4 hours' duration, HK-II cytosolic activity, protein content, and mRNA levels increase by 50% to 200% in healthy nondiabetic subjects, and this is associated with the translocation of hexokinase II from the cytosol to the mitochondria.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.7. Glucose Phosphorylation
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Because the number of GLUT4 transporters in the muscle of diabetic subjects is normal, impaired GLUT4 translocation and decreased intrinsic activity of the glucose transporter must be responsible for the defect in muscle glucose transport.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.6. Glucose Transport
boosteddirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Nonetheless, these studies are consistent in demonstrating that abnormalities in both muscle glucose phosphorylation and glucose transport are well established early in the natural history of type 2 diabetes and cannot be explained by glucose toxicity.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.7. Glucose Phosphorylation
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“In human skeletal muscle, HK-II transcription is regulated by insulin, whereas HK-I mRNA and protein levels are not affected by insulin [199, 200].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.7. Glucose Phosphorylation
What the sources say
- Not checked yetcites [199] Vogt C Ardehali H Iozzo P Regulation of hexokinase II expression in human skeletal muscle in vivo Metabolism 2000 49 6 814 818 10877213 source
- Not checked yetcites [200] Pendergrass M Koval J Vogt C Insulin-induced hexokinase II expression is reduced in obesity and NIDDM Diabetes 1998 47 3 387 394 9519744 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Studies using 31P nuclear magnetic resonance in combination with [1-14C] glucose also have demonstrated that both insulin-stimulated muscle glucose transport and glucose phosphorylation are impaired in type 2 diabetic subjects, but the defect in transport exceeds the defect in phosphorylation [194].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.7. Glucose Phosphorylation
What the sources say
- Not checked yetcites [194] Cline GW Petersen KF Krssak M Impaired glucose transport as a cause of decreased insulin-stimulated muscle glycogen synthesis in type 2 diabetes The New England Journal of Medicine 1999 341 4 240 246 10413736 source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The regulatory subunit of PP1 has two serine phosphorylation sites, called site 1 and site 2. Phosphorylation of site 2 by cAMP-dependent protein kinase inactivates PP1; whereas phosphorylation of site 1 by insulin activates PP1, leading to the stimulation of glycogen synthase.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.8. Glycogen Synthesis
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“In forearm muscle, insulin-stimulated glucose transport (measured with the triple-tracer technique) is markedly impaired in lean type 2 diabetics [192, 193], but the rate of intracellular glucose phosphorylation is impaired to an even greater extent, resulting in an increase in the free glucose concentration within the intracellular space that is accessible to glucose.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.7. Glucose Phosphorylation
What the sources say
- Not checked yetcites [192] Bonadonna RC Del Prato S Saccomani MP Transmembrane glucose transport in skeletal muscle of patients with non-insulin-dependent diabetes The Journal of Clinical Investigation 1993 92 1 486 494 8326013 PMC293636 source
- Not checked yetcites [193] Bonadonna RC Del Prato S Bonora E Roles of glucose transport and glucose phosphorylation in muscle insulin resistance of NIDDM Diabetes 1996 45 supplement 3 915 925 8666143 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“GLUT4, the insulin regulatable transporter, is found in skeletal muscle, has a Km of approximately 5 mmol/L, which is close to that of the plasma glucose concentration, and is associated with HK-II [173, 174].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.6. Glucose Transport
What the sources say
- Not checked yetcites [173] Yu C Chen Y Cline GW Mechanism by which fatty acids inhibit insulin activation of insulin receptor substrate-1 (IRS-1)-associated phosphatidylinositol 3-kinase activity in muscle The Journal of Biological Chemistry 2002 277 52 50230 50236 12006582 source
- Not checked yetcites [174] Schmitz-Peiffer C Browne CL Oakes ND Alterations in the expression and cellular localization of protein kinase C isozymes ε and θ are associated with insulin resistance in skeletal muscle of the high-fat-fed rat Diabetes 1997 46 2 169 178 9000691 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The impairment in glycogen synthase activation is likely due to a defect in the ability of insulin to phosphorylate IRS-1, causing a reduced association of the p85 subunit of PI 3-kinase with IRS-1 and decreased activation of the enzyme PI3K.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 5. Summary
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Glycogen synthase mRNA and protein levels, however, are decreased in muscle of type 2 diabetic patients, partly explaining the decreased glycogen synthase activity [221, 222].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.8. Glycogen Synthesis
What the sources say
- Not checked yetcites [221] Vestergaard H Lund S Larsen FS Bjerrum OJ Pedersen O Glycogen synthase and phosphofructokinase protein and mRNA levels in skeletal muscle from insulin-resistant patients with non-insulin-dependent diabetes mellitus The Journal of Clinical Investigation 1993 91 6 2342 2350 8514849 PMC443291 source
- Not checked yetcites [222] Vestergaard H Bjorbaek C Andersen PH Bak JF Pedersen O Impaired expression of glycogen synthase mRNA in skeletal muscle of NIDDM patients Diabetes 1991 40 12 1740 1745 1756915 source
plainconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Several silent nucleotide substitutions were found in the PP1 and ISPK-1 genes in the Danish population”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.8. Glycogen Synthesis
What the sources say
- Not checked yetcites [226] Bjørbæk C Vik TA Echwald SM Cloning of a human insulin-stimulated protein kinase (ISPK-1) gene and analysis of coding regions and mRNA levels of the ISPK-1 and the protein phosphatase-1 genes in muscle from NIDDM patients Diabetes 1995 44 1 90 97 7813820 source
- Not checked yetcites [227] Prochazka M Mochizuki H Baier LJ Cohen PTW Bogardus C Molecular and linkage analysis of type-1 protein phosphatase catalytic beta-subunit gene: lack of evidence for its major role in insulin a resistance in Pima Indians Diabetologia 1995 38 4 461 466 7796987 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The quote only partly states this claim.
In the paper
“Insulin has no effect on muscle PFK activity, mRNA levels, or protein content in either nondiabetic or diabetic individuals [221].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.9. Glycolysis
What the sources say
- Not checked yetcites [221] Vestergaard H Lund S Larsen FS Bjerrum OJ Pedersen O Glycogen synthase and phosphofructokinase protein and mRNA levels in skeletal muscle from insulin-resistant patients with non-insulin-dependent diabetes mellitus The Journal of Clinical Investigation 1993 91 6 2342 2350 8514849 PMC443291 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Under basal conditions, total glycogen synthase activity in type 2 diabetic subjects is reduced, and the ability of insulin to activate glycogen synthase is severely impaired [7, 215–217].”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.8. Glycogen Synthesis
What the sources say
- Not checked yetcites [7] Cusi K Maezono K Osman A Insulin resistance differentially affects the PI 3-kinase- and MAP kinase-mediated signaling in human muscle The Journal of Clinical Investigation 2000 105 3 311 320 10675357 PMC377440 source
- Not checked yetcites [215] Damsbo P Vaag A Hother-Nielsen O Beck-Nielsen H Reduced glycogen synthase activity in skeletal muscle from obese patients with and without type 2 (non-insulin-dependent) diabetes mellitus Diabetologia 1991 34 4 239 245 1906024 source
- Not checked yetcites [216] Mandarino LJ Wright KS Verity LS Effects of insulin infusion on human skeletal muscle pyruvate dehydrogenase, phosphofructokinase, and glycogen synthase: evidence for their role in oxidative and nonoxidative glucose metabolism The Journal of Clinical Investigation 1987 80 3 655 663 2957389 PMC442287 source
- Not checked yetcites [217] Thorburn AW Gumbiner B Bulacan F Wallace P Henry RR Intracellular glucose oxidation and glycogen synthase activity are reduced in non-insulin-dependent (type II) diabetes independent of impaired glucose uptake The Journal of Clinical Investigation 1990 85 2 522 529 2105341 PMC296454 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper relies on this without support.
Basal and insulin-stimulated glucose oxidation rates are not reduced in normal glucose-tolerant offspring of two diabetic parents and in first-degree relatives of type 2 diabetic subjects, but are decreased in overtly diabetic subjects.
“Consistent with this scenario, the rates of basal and insulin-stimulated glucose oxidation are not reduced in the normal glucose-tolerant offspring of two diabetic parents and in the first-degree relatives of type 2 diabetic subjects; whereas they are decreased in overtly diabetic subjects.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Therefore, any impairments occur on main phosphorylation sites will reduce insulin receptor tyrosine kinase activity, eventually affecting the insulin function (88–90).”
From Diabetes and Sarcopenic Obesity: Pathogenesis, Diagnosis, and Treatments (2020) · cites this paper as [88]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.4. Insulin Receptor Tyrosine Kinase Activity
“In insulin-resistant obese nondiabetic subjects, in the NGT insulin resistant offspring of two diabetic parents, and in type 2 diabetic subjects, a substantial decrease in insulin receptor tyrosine phosphorylation has been demonstrated.”
§ Pathogenesis of Insulin Resistance in Skeletal Muscle > 4. Cellular Mechanism of Insulin Resistance > 4.4. Insulin Receptor Tyrosine Kinase Activity
“However, when insulin-stimulated insulin receptor tyrosine phosphorylation was examined in normal-glucose-tolerant insulin-resistant individuals (offspring of two diabetic parents) at high risk for developing type 2 diabetes, a normal increase in tyrosine phosphorylation of the insulin receptor was observed [164].”
Citations
Cites
2 retracted
Insulin Binding to Monocytes and Insulin Action in Human Obesity, Starvation, and Refeeding
Defronzo, R. A., Soman, V., Sherwin, R. S., Hendler, R., & Felig, P. (1978) · Journal of Clinical Investigation · doi:10.1172/jci109108 · Cited by 252
Self-citationRetractedInsulin Sensitivity and Insulin Binding to Monocytes in Maturity-Onset Diabetes
Defronzo, R., Deibert, D., Hendler, R., Felig, P., & Soman, V. (1979) · Journal of Clinical Investigation · doi:10.1172/jci109394 · Cited by 188
Self-citationRetractedRole of Insulin Resistance in Human Disease
Reaven, G. M. (1988) · Diabetes · doi:10.2337/diab.37.12.1595 · Cited by 12,154
Mechanisms linking obesity to insulin resistance and type 2 diabetes
Kahn, S. E., Hull, R. L., & Utzschneider, K. M. (2006) · Nature · doi:10.1038/nature05482 · Cited by 5,448
Insulin signalling and the regulation of glucose and lipid metabolism
Saltiel, A. R., & Kahn, C. R. (2001) · Nature · doi:10.1038/414799a · Cited by 5,326
Randle, P. J., Garland, P. B., Hales, C. N., & Newsholme, E. A. (1963) · The Lancet · doi:10.1016/s0140-6736(63)91500-9 · Cited by 5,093
Yamauchi, T., Kamon, J., Waki, H., Terauchi, Y., Kubota, N., Hara, K., Mori, Y., Ide, T., Murakami, K., Tsuboyama-Kasaoka, N., et al. (2001) · Nature Medicine · doi:10.1038/90984 · Cited by 4,915
DeFronzo, R. A., & Ferrannini, E. (1991) · Diabetes Care · doi:10.2337/diacare.14.3.173 · Cited by 4,555
Self-citationLagouge, M., Argmann, C., Gerhart-Hines, Z., Meziane, H., Lerin, C., Daussin, F., Messadeq, N., Milne, J., Lambert, P., Elliott, P., et al. (2006) · Cell · doi:10.1016/j.cell.2006.11.013 · Cited by 4,057
DeFronzo, R. A. (2009) · Diabetes · doi:10.2337/db09-9028 · Cited by 3,016
Self-citation
Research works printed but not linked: 25
- 1997, Diabetes Reviews, 5, 177
- 1939, Clinical Science, 4, 120
- 1994, Diabetes Reviews, 2, 29
- 1996, Journal of Hypertension, 14, 489
- 1982, International Journal of Obesity, 6, 73
- 1990, Current Opinion in Cardiology, 5, 586
- 1999, American Journal of Physiology, 276, E352
- 2003, American Journal of Physiology, 284, E741
- 2007, Diabetes, 56
- 2008, Diabetes, 56
- 2002, Diabetes, 51, 144, 10.2337/diabetes.51.1.144 · DOI · Paper page
- 1984, Journal of Applied Physiology Respiratory Environmental and Exercise Physiology, 56, 831
- 2007, Diabetes, 56
- 1994, Biochemical Journal, 267, 303
- 2001, Diabetes, 50, 2572
- 1999, The Journal of Clinical Investigation, 103, 253, 10.1172/JCI5001 · DOI · Paper page
- 10.1074/jbc.M200958200 · DOI · Paper page
- 1997, American Journal of Physiology, 273, E915
- 1999, American Journal of Cardiology, 84, 21J
- 2002, American Journal of Physiology, 282, E974
- 2000, Diabetes, 49, 284, 10.2337/diabetes.49.2.284 · DOI · Paper page
- 2001, American Journal of Physiology, 281, E72
- 1995, American Journal of Physiology, 269, E701
- 1986, American Journal of Physiology, 251, E489
- 1992, American Journal of Physiology, 263, E79
Cited by
Sorted by citations
Pathophysiology of type 2 diabetes mellitus
Galicia-Garcia, U., Benito-Vicente, A., Jebari, S., Larrea-Sebal, A., Siddiqi, H., Uribe, K. B., Ostolaza, H., & Martín, C. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21176275 · Cited by 3,360
“Thus, mutations in any of the main phosphorylation sites can impair INSR tyrosine kinase activity, thereby impairing insulin action on skeletal muscle [161].”
BackgroundTalbot, K., Wang, H.-Y., Kazi, H., Han, L.-Y., Bakshi, K. P., Stucky, A., Fuino, R. L., Kawaguchi, K. R., Samoyedny, A. J., Wilson, R. S., et al. (2012) · Journal of Clinical Investigation · doi:10.1172/jci59903 · Cited by 1,871
Mechanisms Linking Inflammation to Insulin Resistance
Chen, L., Chen, R., Wang, H., & Liang, F. (2015) · International Journal of Endocrinology · doi:10.1155/2015/508409 · Cited by 644
Hong, S.-H., & Choi, K. M. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21020494 · Cited by 390
Gut microbiota, probiotics and diabetes
Gomes, A. C., Bueno, A. A., de Souza, R. G. M., & Mota, J. F. (2014) · Nutrition Journal · doi:10.1186/1475-2891-13-60 · Cited by 363
Metadata
- Authors
- Abdul-Ghani, M. A., & DeFronzo, R. A.
- Affiliations
- Division of Diabetes, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229, USA
- The University of Texas at San Antonio Health Science Center (US)
- ORCID
- DeFronzo, Ralph A.
- Venue
- Journal of Biomedicine and Biotechnology
- Publisher
- Hindawi Limited
- Published
- 2010
- Volume
- 2010
- Pages
- 1-19
- ISSN
- 1110-7243 (ISSN-L)
- 1110-7251
- PMC
- PMC2860140
- OpenAlex
- W2033524876
- Semantic Scholar
- ae0836fd0213314956d83d1c268fc71c268be37f
- Cited by
- 670
- References
- 236
- Citations by year
- 2026: 28 · 2025: 40 · 2024: 46 · 2023: 57 · 2022: 55 · 2021: 56 · 2020: 47 · 2019: 38 · 2018: 44 · 2017: 42 · 2016: 43 · 2015: 38 · 2014: 36 · 2013: 32 · 2012: 38
- FWCI
- 2.78
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- BioMed Research International (publishedVersion, cc-by)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- insulin resistance, skeletal muscle, insulin signaling, glucose uptake, glucose transport, glucose phosphorylation, glycogen synthesis, glucose oxidation, type 2 diabetes, obesity, metabolic syndrome, fatty acid metabolism, mitochondrial dysfunction, oxidative phosphorylation
- MeSH terms
- Animals, Humans, Insulin Resistance, Muscle, Skeletal
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-06, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-06 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
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