Reduced mitochondrial density and increased IRS-1 serine phosphorylation in muscle of insulin-resistant offspring of type 2 diabetic parents
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To further explore the nature of the mitochondrial dysfunction and insulin resistance that occur in the muscle of young, lean, normoglycemic, insulin-resistant offspring of parents with type 2 diabetes (IR offspring), we measured mitochondrial content by electron microscopy and insulin signaling in muscle biopsy samples obtained from these individuals before and during a hyperinsulinemic-euglycemic clamp. The rate of insulin-stimulated muscle glucose uptake was approximately 60% lower in the IR offspring than the control subjects and was associated with an approximately 60% increase in the intramyocellular lipid content as assessed by H magnetic resonance spectroscopy. Muscle mitochondrial density was 38% lower in the IR offspring. These changes were associated with a 50% increase in IRS-1 Ser312 and IRS-1 Ser636 phosphorylation and an approximately 60% reduction in insulin-stimulated Akt activation in the IR offspring. These data provide new insights into the earliest defects that may be responsible for the development of type 2 diabetes and support the hypothesis that reductions in mitochondrial content result in decreased mitochondrial function, which predisposes IR offspring to intramyocellular lipid accumulation, which in turn activates a serine kinase cascade that leads to defects in insulin signaling and action in muscle.
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Increased serine phosphorylation of IRS-1 impairs insulin signaling in type 2 diabetes.
“Increased serine phosphorylation of IRS-1 has been shown to impair insulin signaling (tyrosine phosphorylation of both insulin resistance and IRS-1) in type 2 diabetes ( 56 ).”
From Skeletal Muscle Insulin Resistance Is the Primary Defect in Type 2 Diabetes (2009) · cites this paper as [56]
The Introduction (page unavailable) describes IRS-1 serine phosphorylation blocking tyrosine phosphorylation of IRS-1 as a proposed mechanism. The Results and Discussion report increased IRS-1 serine phosphorylation alongside reduced Akt activation in insulin-resistant offspring of people with type 2 diabetes. They do not establish that serine phosphorylation caused impaired signaling in patients with type 2 diabetes, or show impaired tyrosine phosphorylation of the insulin receptor itself. (LLM, conf=0.87)
Experimental — accuracy not yet measuredMitochondria from insulin-resistant offspring of type 2 diabetic parents increase ATP production by only 5% in response to insulin, compared with 90% in NGT subjects without a family history of diabetes.
“Whereas mitochondria from NGT subjects without any family history of diabetes responded to insulin by increasing ATP production by 90%, mitochondria from insulin-resistant offspring increased ATP production by only 5% (Fig. A13).”
From Skeletal Muscle Insulin Resistance Is the Primary Defect in Type 2 Diabetes (2009) · cites this paper as [57]
The Discussion (page not provided) reports that a previous study found about 30% lower skeletal-muscle mitochondrial ATP production in a similar group of insulin-resistant offspring. It does not report ATP-production increases of 5% and 90% in response to insulin, so it supports the general difference between groups but not the claimed insulin-response comparison. (LLM, conf=0.78)
Experimental — accuracy not yet measuredIn lean insulin-resistant NGT offspring of type 2 diabetic parents, increased serine phosphorylation of IRS-1 in skeletal muscle is associated with impaired activation of Akt.
“In lean insulin-resistant NGT offspring of type 2 diabetic parents, increased serine phosphorylation of IRS-1 in skeletal muscle has been documented in association with impaired activation of Akt ( 57 ) (Fig. A11).”
From Skeletal Muscle Insulin Resistance Is the Primary Defect in Type 2 Diabetes (2009) · cites this paper as [57]
Mitochondrial mass is 14-38% lower in muscle in obesity and type 2 diabetes.
“Mitochondrial mass is consistently 14–38% lower in muscle in obesity and type 2 diabetes (2–5).”
Electron microscopic studies show an approximately 40% reduction in mitochondrial density in skeletal muscle in lean normal-glucose-tolerant offspring of type 2 diabetic parents, obese non-diabetic individuals, and type 2 diabetic subjects compared with lean insulin-sensitive age-matched controls.
“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].”
From Pathogenesis of insulin resistance in skeletal muscle (2010) · cites this paper as [111]
Rodent and human studies suggest increased serine phosphorylation of IRS-1 in insulin-resistant states.
“Rodent and human studies have suggested increased serine phosphorylation of IRS-1 in insulin resistant states [111, 171–173].”
From Pathogenesis of insulin resistance in skeletal muscle (2010) · cites this paper as [111]
Additional studies confirmed that mitochondrial content is decreased and many factors regulating mitochondria are altered in obese, insulin-resistant adults and offspring of parents with type 2 diabetes.
“Additional studies confirmed that mitochondrial content is decreased and many factors regulating mitochondria are altered in obese, insulin-resistant adults as well as the offspring of parents with T2D (33,(78)(79)(80)(81)(82).”
From Altered mitochondrial function in insulin-deficient and insulin-resistant states (2018) · cites this paper as [79]
Aging and obesity/diabetes share physiological aspects including accumulation of ectopic lipids and lipotoxicity in liver, skeletal muscle and heart, as well as decreased mitochondrial number and activity.
“A number of physiological aspects of aging are also found in obesity and diabetes (Fig. 2) including accumulation of ectopic lipids and lipotoxicity in metabolic organs such as liver, skeletal muscle and heart, as well as decreased mitochondrial number and activity [144–147].”
From Targeting Intramyocellular Lipids to Improve Aging Muscle Function (2025) · cites this paper as [146]
In this cohort, a reduction in mitochondrial content probably accounts for the reduced rate of oxidative phosphorylation in mitochondria.
“Thus, at least in this cohort, a reduction in mitochondrial content probably accounted for the reduced rate of oxidative phosphorylation in mitochondria.”
From Lipid-induced insulin resistance: unravelling the mechanism (2010) · cites this paper as [44]
Similar reductions in OXPHOS gene expression have been observed in some, but not all, populations of insulin-resistant, but completely normoglycemic, individuals.
“Importantly, similar reductions in OXPHOS gene expression have been observed in some, but not all, populations of insulin-resistant, but completely normoglycemic, individuals (122, 124).”
From The role of mitochondria in the pathogenesis of type 2 diabetes (2010) · cites this paper as [124]
Alterations in muscle PGC-1α and -β mRNA expression are observed in humans with insulin resistance-being reduced by nearly 50% in muscle from individuals with diabetes and in some populations of normoglycemic insulin-resistant humans.
“Moreover, alterations in muscle PGC-1␣ and - mRNA expression are observed in humans with insulin resistance-being reduced by nearly 50% in muscle from individuals with diabetes (122, 145) and in some populations of normoglycemic insulin-resistant humans (121, 124, 137).”
From The role of mitochondria in the pathogenesis of type 2 diabetes (2010) · cites this paper as [124]
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Cites
Mootha, V. K., Lindgren, C. M., Eriksson, K.-F., Subramanian, A., Sihag, S., Lehar, J., Puigserver, P., Carlsson, E., Ridderstråle, M., Laurila, E., et al. (2003) · Nature Genetics · doi:10.1038/ng1180 · Cited by 10,197 · see citing works
Matsuda, M., & DeFronzo, R. A. (1999) · Diabetes Care · doi:10.2337/diacare.22.9.1462 · Cited by 5,621 · see citing works
A short questionnaire for the measurement of habitual physical activity in epidemiological studies
Baecke, J. A. H., BUREMA, J., & Frijters, J. E. R. (1982) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/36.5.936 · Cited by 3,950 · see citing works
Mutation of the mouse klotho gene leads to a syndrome resembling ageing
Kuro-o, M., Matsumura, Y., Aizawa, H., Kawaguchi, H., Suga, T., Utsugi, T., Ohyama, Y., Kurabayashi, M., Kaname, T., Kume, E., et al. (1997) · Nature · doi:10.1038/36285 · Cited by 3,837 · see citing works
Mechanisms of fatty acid-induced inhibition of glucose uptake.
Boden, G., Chen, X., Ruiz, J., White, J. V., & Rossetti, L. (1994) · Journal of Clinical Investigation · doi:10.1172/jci117252 · Cited by 3,702 · see citing works
Watterson, K. R., Bestow, D., Gallagher, J. R., Hamilton, D. L., Ashford, F. B., Meakin, P. J., & Ashford, M. L. J. (2012) · Neurosignals · doi:10.1159/000334144 · Cited by 3,395 · see citing works
A central role for JNK in obesity and insulin resistance
Hirosumi, J., Tuncman, G., Chang, L., Görgün, C. Z., Uysal, K. T., Maeda, K., Karin, M., & Hotamisligil, G. S. (2002) · Nature · doi:10.1038/nature01137 · Cited by 3,359 · see citing works
Cellular mechanisms of insulin resistance
Shulman, G. I. (2000) · Journal of Clinical Investigation · doi:10.1172/jci10583 · Cited by 2,714 · see citing works
Impaired Mitochondrial Activity in the Insulin-Resistant Offspring of Patients with Type 2 Diabetes
Petersen, K. F., Dufour, S., Befroy, D., Garcia, R., & Shulman, G. I. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa031314 · Cited by 2,193 · see citing works
Patti, M. E., Butte, A. J., Crunkhorn, S., Cusi, K., Berria, R., Kashyap, S., Miyazaki, Y., Kohane, I., Costello, M., Saccone, R., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1032913100 · Cited by 1,952 · see citing works
Absence of S6K1 protects against age- and diet-induced obesity while enhancing insulin sensitivity
Um, S. H., Frigerio, F., Watanabe, M., Picard, F., Joaquin, M., Sticker, M., Fumagalli, S., Allegrini, P. R., Kozma, S. C., Auwerx, J., et al. (2004) · Nature · doi:10.1038/nature02866 · Cited by 1,677 · see citing works
Yu, C., Chen, Y., Cline, G. W., Zhang, D., Zong, H., Wang, Y., Bergeron, R., Kim, J. K., Cushman, S. W., Cooney, G. J., et al. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m200958200 · Cited by 1,561 · see citing works
Itani, S. I., Ruderman, N. B., Schmieder, F., & Boden, G. (2002) · Diabetes · doi:10.2337/diabetes.51.7.2005 · Cited by 1,390 · see citing works
Mechanism of hepatic insulin resistance in non-alcoholic fatty liver disease
Samuel, V. T., Liu, Z.-X., Qu, X., Elder, B. D., Bilz, S., Befroy, D., Romanelli, A. J., & Shulman, G. I. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m313478200 · Cited by 1,322 · see citing works
Dresner, A., Laurent, D., Marcucci, M., Griffin, M. E., Dufour, S., Cline, G. W., Slezak, L. A., Andersen, D. K., Hundal, R. S., Rothman, D. L., et al. (1999) · Journal of Clinical Investigation · doi:10.1172/jci5001 · Cited by 1,311 · see citing works
Griffin, M. E., Marcucci, M. J., Cline, G. W., Bell, K., Barucci, N., Lee, D., Goodyear, L. J., Kraegen, E. W., White, M. F., & Shulman, G. I. (1999) · Diabetes · doi:10.2337/diabetes.48.6.1270 · Cited by 1,267 · see citing works
Krssak, M., Falk Petersen, K., Dresner, A., DiPietro, L., Vogel, S. M., Rothman, D. L., Shulman, G. I., & Roden, M. (1999) · Diabetologia · doi:10.1007/s001250051123 · Cited by 1,264 · see citing works
Zong, H., Ren, J. M., Young, L. H., Pypaert, M., Mu, J., Birnbaum, M. J., & Shulman, G. I. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.252625599 · Cited by 1,036 · see citing works
Aguirre, V., Werner, E. D., Giraud, J., Lee, Y. H., Shoelson, S. E., & White, M. F. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m101521200 · Cited by 1,010 · see citing works
Deficiency of subsarcolemmal mitochondria in obesity and type 2 diabetes
Ritov, V. B., Menshikova, E. V., He, J., Ferrell, R. E., Goodpaster, B. H., & Kelley, D. E. (2005) · Diabetes · doi:10.2337/diabetes.54.1.8 · Cited by 887 · see citing works
Perseghin, G., Scifo, P., De Cobelli, F., Pagliato, E., Battezzati, A., Arcelloni, C., Vanzulli, A., Testolin, G., Pozza, G., Del Maschio, A., et al. (1999) · Diabetes · doi:10.2337/diabetes.48.8.1600 · Cited by 877 · see citing works
Tissue-specific overexpression of lipoprotein lipase causes tissue-specific insulin resistance
Kim, J. K., Fillmore, J. J., Chen, Y., Yu, C., Moore, I. K., Pypaert, M., Lutz, E. P., Kako, Y., Velez-Carrasco, W., Goldberg, I. J., et al. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.121164498 · Cited by 753 · see citing works
Prevention of fat-induced insulin resistance by salicylate
Kim, J. K., Kim, Y.-J., Fillmore, J. J., Chen, Y., Moore, I., Lee, J., Yuan, M., Li, Z. W., Karin, M., Perret, P., et al. (2001) · Journal of Clinical Investigation · doi:10.1172/jci11559 · Cited by 737 · see citing works
Measurement of intracellular triglyceride stores by H spectroscopy: validation in vivo
Szczepaniak, L. S., Babcock, E. E., Schick, F., Dobbins, R. L., Garg, A., Burns, D. K., McGarry, J. D., & Stein, D. T. (1999) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1999.276.5.e977 · Cited by 688 · see citing works
Cline, G. W., Petersen, K. F., Krssak, M., Shen, J., Hundal, R. S., Trajanoski, Z., Inzucchi, S., Dresner, A., Rothman, D. L., & Shulman, G. I. (1999) · New England Journal of Medicine · doi:10.1056/nejm199907223410404 · Cited by 675 · see citing works
Mayerson, A. B., Hundal, R. S., Dufour, S., Lebon, V., Befroy, D., Cline, G. W., Enocksson, S., Inzucchi, S. E., Shulman, G. I., & Petersen, K. F. (2002) · Diabetes · doi:10.2337/diabetes.51.3.797 · Cited by 647 · see citing works
Development of Muscle Insulin Resistance After Liver Insulin Resistance in High-Fat–Fed Rats
Kraegen, E. W., Clark, P. W., Jenkins, A. B., Daley, E. A., Chisholm, D. J., & Storlien, L. H. (1991) · Diabetes · doi:10.2337/diab.40.11.1397 · Cited by 601 · cited 1× · see citing works
“These data are consistent with those of previous studies in humans (7, 16, 17) and rodents (18, 19), which have suggested that dysregulated intramuscular fatty acid metabolism has an important causative role in insulin resistance and may have a similar role in fat-induced insulin resistance in the…”
Stump, C. S., Short, K. R., Bigelow, M. L., Schimke, J. M., & Nair, K. S. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1332551100 · Cited by 477 · see citing works
A microfluorometric method for the determination of free fatty acids in plasma
Miles, J., Glasscock, R., Aikens, J., Gerich, J. E., & Haymond, M. W. (1983) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)38029-9 · Cited by 329 · see citing works
Bouzakri, K., Roques, M., Gual, P., Espinosa, S., Guebre-Egziabher, F., Riou, J.-P., Laville, M., Le Marchand-Brustel, Y., Tanti, J.-F., & Vidal, H. (2003) · Diabetes · doi:10.2337/diabetes.52.6.1319 · Cited by 305 · see citing works
Ling, C., Poulsen, P., Carlsson, E., Ridderstråle, M., Almgren, P., Wojtaszewski, J. F. P., Beck‐Nielsen, H., Groop, L., & Vaag, A. A. (2004) · Journal of Clinical Investigation · doi:10.1172/jci200421889 · Cited by 300 · see citing works
Ling, C., Poulsen, P., Carlsson, E., Ridderstråle, M., Almgren, P., Wojtaszewski, J., Beck-Nielsen, H., Groop, L., & Vaag, A. (2004) · Journal of Clinical Investigation · doi:10.1172/jci21889 · Cited by 300 · see citing works
Metabolic Effects of Troglitazone Monotherapy in Type 2 Diabetes Mellitus
Maggs, D. G., Buchanan, T. A., Burant, C., Cline, G. W., Gumbiner, B., Hsueh, W. A., Inzucchi, S., Kelley, D., Nolan, J., Olefsky, J. M., et al. (1998) · Annals of Internal Medicine · doi:10.7326/0003-4819-128-3-199802010-00002 · Cited by 286 · see citing works
Gene Expression Profile in Skeletal Muscle of Type 2 Diabetes and the Effect of Insulin Treatment
Sreekumar, R., Halvatsiotis, P., Schimke, J. C., & Nair, K. S. (2002) · Diabetes · doi:10.2337/diabetes.51.6.1913 · Cited by 257 · see citing works
Fea, K. D., & Roth, R. A. (1997) · Biochemistry · doi:10.1021/bi971157f · Cited by 246 · see citing works
Kelley, D. E., Mintun, M. A., Watkins, S. C., Simoneau, J. A., Jadali, F., Fredrickson, A., Beattie, J., & Thériault, R. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118724 · Cited by 228 · see citing works
Paz, K., Liu, Y., Shorer, H., Hemi, R., LeRoith, D., Quan, M., Kanety, H., Seger, R., & Zick, Y. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.40.28816 · Cited by 191 · see citing works
Development of muscle insulin resistance after liver insulin resistance in high-fat-fed rats
Kraegen, E. W., Clark, P. W., Jenkins, A. B., et al. (1991) · Diabetes · doi:10.2337/diabetes.40.11.1397 · Cited by 100 · see citing works
Prevention of fat-induced insulin resistance by salicylate
Kim, J. K., Kim, Y. J., Fillmore, J. J., et al. (2001) · Journal of Clinical Investigation · doi:10.1172/jci200111559 · Cited by 80 · see citing works
Diamond, M. P., Jacob, R. J., Connolly-Diamond, M., & DeFronzo, R. A. (1993) · PubMed · Cited by 35 · see citing works
Bhat, H. K., & Epelboym, I. (2004) · Journal of Biochemical and Molecular Toxicology · doi:10.1002/jbt.20024 · Cited by 27 · see citing works
Paz, K., Liu, Y., Shorer, H., Hemi, R., LeRoith, D., Quon, M. J., Kanety, H., Seger, R., & Zick, Y. (1999) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)51589-7 · Cited by 17 · see citing works
Flagged first, then by citations
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DeFronzo, R. A. (2009) · Diabetes · doi:10.2337/db09-9028 · Cited by 3,016 · see citing works
DeFronzo, R. A., Ferrannini, E., Groop, L., Henry, R. R., Herman, W. H., Holst, J. J., Hu, F. B., Kahn, C. R., Raz, I., Shulman, G. I., et al. (2015) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2015.19 · Cited by 2,611 · see citing works
Skeletal Muscle Insulin Resistance Is the Primary Defect in Type 2 Diabetes
DeFronzo, R. A., & Tripathy, D. (2009) · Diabetes Care · doi:10.2337/dc09-s302 · Cited by 2,102 · see citing works
Bhatti, J. S., Bhatti, G. K., & Reddy, P. H. (2017) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2016.11.010 · Cited by 1,655 · see citing works
The pathogenesis of insulin resistance: integrating signaling pathways and substrate flux
Samuel, V. T., & Shulman, G. I. (2016) · Journal of Clinical Investigation · doi:10.1172/jci77812 · Cited by 1,484 · see citing works
PGC-1 coactivators: inducible regulators of energy metabolism in health and disease
Finck, B. N. (2006) · Journal of Clinical Investigation · doi:10.1172/jci27794 · Cited by 1,427 · see citing works
Oxidative stress, insulin signaling, and diabetes
Rains, J., & Jain, S. K. (2010) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2010.12.006 · Cited by 1,444 · see citing works
Pathogenesis of type 2 diabetes mellitus
DeFronzo, R. A. (2004) · Medical Clinics of North America · doi:10.1016/j.mcna.2004.04.013 · Cited by 1,342 · see citing works
The role of estrogens in control of energy balance and glucose homeostasis
Mauvais-Jarvis, F., Clegg, D. J., & Hevener, A. L. (2013) · Endocrine Reviews · doi:10.1210/er.2012-1055 · Cited by 1,329 · see citing works
PGC-1α: a key regulator of energy metabolism
Liang, H., & Ward, W. F. (2006) · AJP Advances in Physiology Education · doi:10.1152/advan.00052.2006 · Cited by 1,250 · see citing works
Akt signalling in health and disease
Hers, I., Vincent, E. E., & Tavaré, J. M. (2011) · Cellular Signalling · doi:10.1016/j.cellsig.2011.05.004 · Cited by 1,246 · see citing works
Lipid-induced insulin resistance: unravelling the mechanism
Samuel, V. T., Petersen, K. F., & Shulman, G. I. (2010) · The Lancet · doi:10.1016/s0140-6736(10)60408-4 · Cited by 1,189 · see citing works
Chronic Adipose Tissue Inflammation Linking Obesity to Insulin Resistance and Type 2 Diabetes
Zatterale, F., Longo, M., Naderi, J., Raciti, G. A., Desiderio, A., Miele, C., & Beguinot, F. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2019.01607 · Cited by 1,180 · see citing works
Ectopic Fat in Insulin Resistance, Dyslipidemia, and Cardiometabolic Disease
Shulman, G. I. (2014) · New England Journal of Medicine · doi:10.1056/nejmra1011035 · Cited by 1,126 · see citing works
Regulation of mitochondrial biogenesis
Jornayvaz, F. R., & Shulman, G. I. (2010) · Essays in Biochemistry · doi:10.1042/bse0470069 · Cited by 1,119 · see citing works
Disordered lipid metabolism and the pathogenesis of insulin resistance.
Savage, D. B., Petersen, K. F., & Shulman, G. I. (2007) · Physiological Reviews · doi:10.1152/physrev.00024.2006 · Cited by 1,107 · see citing works
AMP-activated protein kinase signaling in metabolic regulation
Long, Y. C. (2006) · Journal of Clinical Investigation · doi:10.1172/jci29044 · Cited by 1,097 · see citing works
Role of Mitochondrial Dysfunction in Insulin Resistance
Kim, J.-A., Wei, Y., & Sowers, J. R. (2008) · Circulation Research · doi:10.1161/circresaha.107.165472 · Cited by 1,103 · see citing works
Handschin, C., & Spiegelman, B. M. (2006) · Endocrine Reviews · doi:10.1210/er.2006-0037 · Cited by 1,090 · see citing works
Koliaki, C., Szendroedi, J., Kaul, K., Jelenik, T., Nowotny, P., Jankowiak, F., Herder, C., Carstensen, M., Krausch, M., Knoefel, W. T., et al. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.04.004 · Cited by 1,032 · see citing works
Copps, K. D., & White, M. F. (2012) · Diabetologia · doi:10.1007/s00125-012-2644-8 · Cited by 1,017 · see citing works
“Given their co-incidence and propensity to aggravate one another, it cannot be stated whether hyperinsulinaemia or dyslipidaemia (or still other factors) underlie increased IRS S/T phosphorylation in the pre-diabetic period [85].”
BackgroundInfluentialMetabolic Flexibility in Health and Disease
Goodpaster, B. H., & Sparks, L. M. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.04.015 · Cited by 995 · see citing works
Cardiovascular Actions of Insulin
Muniyappa, R., Montagnani, M., Koh, K. K., & Quon, M. J. (2007) · Endocrine Reviews · doi:10.1210/er.2007-0006 · Cited by 873 · see citing works
Morino, K., Petersen, K. F., & Shulman, G. I. (2006) · Diabetes · doi:10.2337/db06-s002 · Cited by 853 · see citing works
Self-citationEtiology of Insulin Resistance
Petersen, K. F., & Shulman, G. I. (2006) · The American Journal of Medicine · doi:10.1016/j.amjmed.2006.01.009 · Cited by 825 · see citing works
Adiels, M., Olofsson, S.-O., Taskinen, M.-R., & Borén, J. (2008) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.107.160192 · Cited by 820 · see citing works
Bonnard, C., Durand, A., Peyrol, S., Chanseaume, E., Chauvin, M.-A., Morio, B., Vidal, H., & Rieusset, J. (2008) · Journal of Clinical Investigation · doi:10.1172/jci32601 · Cited by 819 · see citing works
Sivitz, W. I., & Yorek, M. A. (2010) · Antioxidants & Redox Signaling · doi:10.1089/ars.2009.2531 · Cited by 742 · see citing works
Novel biomarkers for pre-diabetes identified by metabolomics
Wang‐Sattler, R., Yu, Z., Herder, C., Messias, A. C., Floegel, A., He, Y., Heim, K., Campillos, M., Holzapfel, C., Thorand, B., et al. (2012) · Molecular Systems Biology · doi:10.1038/msb.2012.43 · Cited by 701 · see citing works
Mechanisms of insulin resistance in obesity
Ye, J. (2013) · Frontiers of Medicine · doi:10.1007/s11684-013-0262-6 · Cited by 699 · see citing works
Pathogenesis of insulin resistance in skeletal muscle
Abdul-Ghani, M. A., & DeFronzo, R. A. (2010) · Journal of Biomedicine and Biotechnology · doi:10.1155/2010/476279 · Cited by 670 · see citing works
Mitochondrial dysfunction in diabetic kidney disease
Forbes, J. M., & Thorburn, D. R. (2018) · Nature Reviews Nephrology · doi:10.1038/nrneph.2018.9 · Cited by 641 · see citing works
The Essential Element Manganese, Oxidative Stress, and Metabolic Diseases: Links and Interactions
Li, L., & Yang, X. (2018) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2018/7580707 · Cited by 660 · see citing works
Non-CpG methylation of the PGC-1α promoter through DNMT3B controls mitochondrial density.
Barrès, R., Osler, M. E., Yan, J., Rune, A., Fritz, T., Caidahl, K., Krook, A., & Zierath, J. R. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2009.07.011 · Cited by 602 · see citing works
The role of mitochondria in insulin resistance and type 2 diabetes mellitus
Szendroedi, J., Phielix, E., & Roden, M. (2012) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2011.138 · Cited by 600 · see citing works
Adams, S. H., Hoppel, C. L., Lok, K. H., Zhao, L., Wong, S. W., Minkler, P. E., Hwang, D. H., Newman, J. W., & Garvey, W. T. (2009) · The Journal of Nutrition · doi:10.3945/jn.108.103754 · Cited by 598 · see citing works
Endothelial dysfunction in diabetes mellitus: Molecular mechanisms and clinical implications
Tabit, C. E., Chung, W. B., Hamburg, N. M., & Vita, J. A. (2010) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-010-9134-4 · Cited by 584 · see citing works
Sarcopenia and type 2 diabetes mellitus: a bidirectional relationship
Mesinovic, J., Zengin, A., de Courten, B. V., Ebeling, P. R., & Scott, D. S. (2019) · Diabetes Metabolic Syndrome and Obesity · doi:10.2147/dmso.s186600 · Cited by 584 · see citing works
The role of mitochondria in the pathogenesis of type 2 diabetes
Patti, M.-E., & Corvera, S. (2010) · Endocrine Reviews · doi:10.1210/er.2009-0027 · Cited by 551 · see citing works
Mitochondrial dysfunction and insulin resistance: an update
Montgomery, M. K., & Turner, N. A. (2014) · Endocrine Connections · doi:10.1530/ec-14-0092 · Cited by 530 · see citing works
Excess Lipid Availability Increases Mitochondrial Fatty Acid Oxidative Capacity in Muscle
Turner, N., Bruce, C. R., Beale, S. M., Hoehn, K. L., So, T., Rolph, M. S., & Cooney, G. J. (2007) · Diabetes · doi:10.2337/db07-0093 · Cited by 520 · see citing works
Patients with type 2 diabetes have normal mitochondrial function in skeletal muscle
Boushel, R., Gnaiger, E., Schjerling, P., Skovbro, M., Kraunsøe, R., & Dela, F. (2007) · Diabetologia · doi:10.1007/s00125-007-0594-3 · Cited by 519 · see citing works
Lipid accumulation in non-adipose tissue and lipotoxicity
van Herpen, N. A., & Schrauwen-Hinderling, V. B. (2008) · Physiology & Behavior · doi:10.1016/j.physbeh.2007.11.049 · Cited by 500 · see citing works
Diacylglycerol-mediated insulin resistance
Erion, D. M., & Shulman, G. I. (2010) · Nature Medicine · doi:10.1038/nm0410-400 · Cited by 493 · see citing works
The potential of endurance exercise-derived exosomes to treat metabolic diseases
Safdar, A., Saleem, A., & Tarnopolsky, M. A. (2016) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2016.76 · Cited by 463 · see citing works
Current views on type 2 diabetes
Lin, Y., & Sun, Z. (2010) · Journal of Endocrinology · doi:10.1677/joe-09-0260 · Cited by 457 · see citing works
Befroy, D. E., Petersen, K. F., Dufour, S., Mason, G. F., de Graaf, R. A., Rothman, D. L., & Shulman, G. I. (2007) · Diabetes · doi:10.2337/db06-0783 · Cited by 453 · see citing works
Metformin Improves Mitochondrial Respiratory Activity through Activation of AMPK
Wang, Y., An, H., Liu, T., Qin, C., Sesaki, H., Guo, S., Radovick, S., Hussain, M., Maheshwari, A., Wondisford, F. E., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.09.070 · Cited by 432 · see citing works
Fiehn, O., Garvey, W. T., Newman, J. W. I., Lok, K. H., Hoppel, C. L., & Adams, S. H. (2010) · PLoS ONE · doi:10.1371/journal.pone.0015234 · Cited by 418 · see citing works
The Role of Skeletal Muscle Glycogen Breakdown for Regulation of Insulin Sensitivity by Exercise
Jensen, J., Rustad, P. I., Kolnes, A. J., & Lai, Y.-C. (2011) · Frontiers in Physiology · doi:10.3389/fphys.2011.00112 · Cited by 412 · see citing works
Villena, J. A. (2014) · FEBS Journal · doi:10.1111/febs.13175 · Cited by 404 · see citing works
Emerging perspectives on essential amino acid metabolism in obesity and the insulin-resistant state
Adams, S. H. (2011) · Advances in Nutrition · doi:10.3945/an.111.000737 · Cited by 394 · see citing works
Mitochondria as key components of the stress response
Manoli, I., Alesci, S., Blackman, M. R., Su, Y. A., Rennert, O. M., & Chrousos, G. P. (2007) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2007.04.004 · Cited by 377 · see citing works
The role of AMP‐activated protein kinase in mitochondrial biogenesis
Reznick, R. M., & Shulman, G. I. (2006) · The Journal of Physiology · doi:10.1113/jphysiol.2006.109512 · Cited by 371 · see citing works
Mitochondrial biogenesis in the metabolic syndrome and cardiovascular disease
Ren, J. T., Pulakat, L., Whaley‐Connell, A. T., & Sowers, J. R. (2010) · Journal of Molecular Medicine · doi:10.1007/s00109-010-0663-9 · Cited by 367 · see citing works
Ectopic fat and insulin resistance: pathophysiology and effect of diet and lifestyle interventions.
Snel, M., Jonker, J. T., Schoones, J., Lamb, H., de Roos, A., Pijl, H., Smit, J. W. A., Meinders, A. E., & Jazet, I. M. (2012) · International Journal of Endocrinology · doi:10.1155/2012/983814 · Cited by 368 · see citing works
Role of Mitochondria in Nonalcoholic Fatty Liver Disease
Nassir, F., & Ibdah, J. A. (2014) · International Journal of Molecular Sciences · doi:10.3390/ijms15058713 · Cited by 359 · see citing works
The metabolic syndrome: role of skeletal muscle metabolism.
Stump, C. S., Henriksen, E. J., Wei, Y., & Sowers, J. R. (2006) · Annals of Medicine · doi:10.1080/07853890600888413 · Cited by 362 · see citing works
Oxidative Stress and Cardiovascular Risk: Obesity, Diabetes, Smoking, and Pollution
Niemann, B., Rohrbach, S., Miller, M. R., Newby, D. E., Fuster, V., & Kovacic, J. C. (2017) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2017.05.043 · Cited by 354 · see citing works
Fyfe, J. J., Bishop, D. J., & Stepto, N. K. (2014) · Sports Medicine · doi:10.1007/s40279-014-0162-1 · Cited by 347 · see citing works
Skeletal muscle lipid deposition and insulin resistance: effect of dietary fatty acids and exercise
Corcoran, M. P., Lamon-Fava, S., & Fielding, R. A. (2007) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/85.3.662 · Cited by 341 · see citing works
Toledo, F. G. S., Menshikova, E. V., Ritov, V. B., Azuma, K., Radikova, Z., DeLany, J., & Kelley, D. E. (2007) · Diabetes · doi:10.2337/db07-0141 · Cited by 321 · see citing works
IRS1-Independent Defects Define Major Nodes of Insulin Resistance
Hoehn, K. L., Hohnen-Behrens, C., Cederberg, A., Wu, L. E., Turner, N. A., Yuasa, T., Ebina, Y., & James, D. E. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2008.04.005 · Cited by 321 · see citing works
Diacylglycerol Activation of Protein Kinase Cε and Hepatic Insulin Resistance
Jornayvaz, F. R., & Shulman, G. I. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.03.005 · Cited by 315 · see citing works
Lee, H.-Y., Choi, C. S., Birkenfeld, A. L., Alves, T. C., Jornayvaz, F. R., Jurczak, M. J., Zhang, D., Woo, D. K., Shadel, G. S., Ladiges, W., et al. (2010) · Cell Metabolism · doi:10.1016/j.cmet.2010.11.004 · Cited by 319 · see citing works
DeFronzo, R. A., & Abdul‐Ghani, M. A. (2011) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2011.03.013 · Cited by 318 · see citing works
BMP4-mediated brown fat-like changes in white adipose tissue alter glucose and energy homeostasis
Qian, S., Tang, Y., Li, X., Liu, Y., Zhang, Y.-Y., Huang, H.-Y., Xue, R.-D., Yu, H.-Y., Guo, L., Gao, H.-D., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1215236110 · Cited by 311 · see citing works
Schrauwen-Hinderling, V. B., Kooi, M. E., Hesselink, M. K. C., Jeneson, J. A. L., Backes, W. H., van Echteld, C. J. A., van Engelshoven, J. M. A., Mensink, M., & Schrauwen, P. (2007) · Diabetologia · doi:10.1007/s00125-006-0475-1 · Cited by 304 · see citing works
Molecular and cellular mechanisms linking inflammation to insulin resistance and β-cell dysfunction
Khodabandehloo, H., Gorgani‐Firuzjaee, S., Panahi, G., & Meshkani, R. (2015) · Translational research · doi:10.1016/j.trsl.2015.08.011 · Cited by 300 · see citing works
Vanweert, F., Schrauwen, P., & Phielix, E. (2022) · Nutrition and Diabetes · doi:10.1038/s41387-022-00213-3 · Cited by 316 · see citing works
Zhang, D., Liu, Z.-X., Choi, C. S., Tian, L., Kibbey, R., Dong, J., Cline, G. W., Wood, P. A., & Shulman, G. I. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0707060104 · Cited by 291 · see citing works
Martins, A. R., Nachbar, R. T., Gorjão, R., Vinolo, M. A. R., Festuccia, W. T., Lambertucci, R. H., Cury‐Boaventura, M. F., Silveira, L. R., Curi, R., & Hirabara, S. M. (2012) · Lipids in Health and Disease · doi:10.1186/1476-511x-11-30 · Cited by 288 · see citing works
Molecular mechanisms of insulin resistance in type 2 diabetes mellitus
Saini, V. (2010) · World Journal of Diabetes · doi:10.4239/wjd.v1.i3.68 · Cited by 292 · see citing works
Sirtuins and Type 2 Diabetes: Role in Inflammation, Oxidative Stress, and Mitochondrial Function
Kitada, M., Ogura, Y., Monno, I., & Koya, D. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00187 · Cited by 289 · see citing works
Ritov, V. B., Menshikova, E. V., Azuma, K., Wood, R., Toledo, F. G. S., Goodpaster, B. H., Ruderman, N. B., & Kelley, D. E. (2010) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00317.2009 · Cited by 283 · see citing works
Corpeleijn, E., Saris, W. H. M., & Blaak, E. E. (2009) · Obesity Reviews · doi:10.1111/j.1467-789x.2008.00544.x · Cited by 280 · see citing works
Choi, C. S., Befroy, D. E., Codella, R., Kim, S., Reznick, R. M., Hwang, Y.-J., Liu, Z.-X., Lee, H.-Y., Distefano, A., Samuel, V. T., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0810339105 · Cited by 279 · see citing works
Zechner, C., Lai, L., Zechner, J. F., Geng, T., Yan, Z., Rumsey, J. W., Collia, D., Chen, Z., Wozniak, D. F., Leone, T. C., et al. (2010) · Cell Metabolism · doi:10.1016/j.cmet.2010.11.008 · Cited by 274 · see citing works
“Significant evidence suggests a link between skeletal muscle mitochondrial dysfunction and the development of insulin resis- tance (Lowell and Shulman, 2005; Morino et al., 2005; Petersen et al., 2005).”
BackgroundÖst, A., Svensson, K., Ruishalme, I., Brännmark, C., Franck, N., Krook, H., Sandström, P., Kjølhede, P., & Strålfors, P. (2010) · Molecular Medicine · doi:10.2119/molmed.2010.00023 · Cited by 271 · see citing works
The Metabolic Basis of Pulmonary Arterial Hypertension
Sutendra, G., & Michelakis, E. D. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.01.004 · Cited by 269 · see citing works
The H19/let-7 double-negative feedback loop contributes to glucose metabolism in muscle cells
Gao, Y., Wu, F., Zhou, J., Yan, L., Jurczak, M. J., Lee, H., Yang, L., Mueller, M., Zhou, X., Dandolo, L., et al. (2014) · Nucleic Acids Research · doi:10.1093/nar/gku1160 · Cited by 269 · see citing works
Zhang, L., Keung, W., Samokhvalov, V., Wang, W. J., & Lopaschuk, G. D. (2009) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2009.09.014 · Cited by 257 · see citing works
Flockhart, M., Nilsson, L. C., Tais, S., Ekblom, B. T., Apró, W., & Larsen, F. J. (2021) · Cell Metabolism · doi:10.1016/j.cmet.2021.02.017 · Cited by 264 · see citing works
Activity-Dependent Signaling Pathways Controlling Muscle Diversity and Plasticity
Schiaffino, S., Sandri, M., & Murgia, M. (2007) · Physiology · doi:10.1152/physiol.00009.2007 · Cited by 251 · see citing works
A Novel MitoTimer Reporter Gene for Mitochondrial Content, Structure, Stress, and Damage in Vivo
Laker, R. C., Xu, P., Ryall, K. A., Sujkowski, A. L., Kenwood, B. M., Chain, K. H., Zhang, M., Royal, M. A., Hoehn, K. L., Driscoll, M., et al. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.530527 · Cited by 254 · see citing works
Fetal Programming and Metabolic Syndrome
Rinaudo, P. F., & Wang, E. T. (2011) · Annual Review of Physiology · doi:10.1146/annurev-physiol-020911-153245 · Cited by 250 · see citing works
Peroxisome Proliferator Activator Receptor γ Coactivator-1 Expression Is Reduced in Obesity
Crunkhorn, S., Dearie, F., Mantzoros, C., Gami, H., da Silva, W. S., Espinoza, D., Faucette, R., Barry, K., Bianco, A. C., & Patti, M. E. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m611214200 · Cited by 236 · see citing works
The role of mitochondria in health and disease
Johannsen, D. L., & Ravussin, É. (2009) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2009.09.002 · Cited by 233 · see citing works
Crawford, S., Hoogeveen, R. C., Brancati, F. L., Astor, B. C., Ballantyne, C. M., Schmidt, M. I., & Young, J. H. (2010) · International Journal of Epidemiology · doi:10.1093/ije/dyq126 · Cited by 230 · see citing works
Lepretti, M., Martucciello, S., Burgos Aceves, M., Putti, R., & Lionetti, L. (2018) · Nutrients · doi:10.3390/nu10030350 · Cited by 232 · see citing works
Tamariz, L. J., Young, J. H., Pankow, J. S., Yeh, H., Schmidt, M. I., Astor, B. C., & Brancati, F. L. (2008) · American Journal of Epidemiology · doi:10.1093/aje/kwn243 · Cited by 221 · see citing works
Mitochondrial Dysfunction, Insulin Resistance, and Potential Genetic Implications
Sangwung, P., Petersen, K. F., Shulman, G. I., & Knowles, J. W. (2020) · Endocrinology · doi:10.1210/endocr/bqaa017 · Cited by 223 · see citing works
Duncan, J. G., Fong, J. L., Medeiros, D. M., Finck, B. N., & Kelly, D. P. (2007) · Circulation · doi:10.1161/circulationaha.106.662296 · Cited by 216 · see citing works
Regulation of Endothelial Function by Mitochondrial Reactive Oxygen Species
Widlansky, M. E., & Gutterman, D. (2011) · Antioxidants and Redox Signaling · doi:10.1089/ars.2010.3642 · Cited by 211 · see citing works
PTMD: A Database of Human Disease-Associated Post-Translational Modifications
Xu, H., Wang, Y., Lin, S., Deng, W., Peng, D., Cui, Q., & Xue, Y. (2018) · Genomics Proteomics & Bioinformatics · doi:10.1016/j.gpb.2018.06.004 · Cited by 208 · see citing works
Metabolic Complications of Childhood Obesity
Weiss, R., & Kaufman, F. R. (2008) · Diabetes Care · doi:10.2337/dc08-s273 · Cited by 209 · see citing works
Skeletal muscle insulin resistance: roles of fatty acid metabolism and exercise
Turcotte, L. P., & Fisher, J. S. (2008) · Physical Therapy · doi:10.2522/ptj.20080018 · Cited by 209 · see citing works
Role of mitochondrial dynamics proteins in the pathophysiology of obesity and type 2 diabetes
Zorzano, A., Liesa, M., & Palacín, M. (2009) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2009.02.004 · Cited by 209 · see citing works
Mitochondrial dysfunction in diabetic cardiomyopathy
Duncan, J. G. (2011) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2011.01.014 · Cited by 209 · see citing works
The coordination of nuclear and mitochondrial communication during aging and calorie restriction
Finley, L. W. S., & Haigis, M. C. (2009) · Ageing Research Reviews · doi:10.1016/j.arr.2009.03.003 · Cited by 207 · see citing works
- Authors
- Morino, K.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Morino, K.
- ORCID
- Morino, K.
- Venue
- Journal of Clinical Investigation
- Published
- 2005-12-01
- Volume
- 115
- Issue
- 12
- Pages
- 3587-3593
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC1280967
- OpenAlex
- W2136942127
- Cited by
- 811
- References
- 40
- Citations by year
- 2026: 6 · 2025: 18 · 2024: 22 · 2023: 32 · 2022: 33 · 2021: 22 · 2020: 41 · 2019: 20 · 2018: 42 · 2017: 40 · 2016: 30 · 2015: 41 · 2014: 50 · 2013: 61 · 2012: 61
- FWCI
- 15.33
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Diabetes Association (DK-49230)
- National Institutes of Health (P30 DK, RR-00125, DK-45735)
- National Institute on Aging (R01AG023686)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01-DK063192, R01DK049230, R01DK040936, P30DK045735, P01DK068229)
- National Center for Research Resources (M01RR000125)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- insulin resistance, type 2 diabetes, offspring of diabetic parents, mitochondrial density, mitochondrial dysfunction, IRS-1 serine phosphorylation, insulin signaling, Akt activation, intramyocellular lipid, muscle glucose uptake, hyperinsulinemic-euglycemic clamp, genetic susceptibility to diabetes
- MeSH terms
- Biopsy, Blood Glucose, Body Weight, Diabetes Mellitus, Type 2, DNA, Mitochondrial, Family Health, Female, Gene Expression Regulation, Glucose Tolerance Test, Humans, Hyperinsulinism, Insulin, Insulin Resistance, Lipids, Male, Microscopy, Electron, Mitochondria, Muscles, Phosphoproteins, Phosphorylation, RNA, Messenger, Serine, Time Factors, Transcription, Genetic, Triglycerides, Blotting, Western, Glucose Clamp Technique, Signal Transduction, Body Mass Index, Protein Serine-Threonine Kinases, Reverse Transcriptase Polymerase Chain Reaction, Microscopy, Electron, Transmission, Immunoprecipitation, Insulin Receptor Substrate Proteins
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