The DOI matches its Crossref record; 42 of the 42 references it cites were found in a registry or an index.
Reduced mitochondrial density and increased IRS-1 serine phosphorylation in muscle of insulin-resistant offspring of type 2 diabetic parents
Open accessAbstract
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“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]
In the citing paper
“Mitochondrial mass is consistently 14–38% lower in muscle in obesity and type 2 diabetes (2–5).”
In the citing 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].”
From Pathogenesis of insulin resistance in skeletal muscle (2010) · cites this paper as [111]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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 the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
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
Matsuda, M., & DeFronzo, R. A. (1999) · Diabetes Care · doi:10.2337/diacare.22.9.1462 · Cited by 5,621
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
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
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 3,720
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
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
Cellular mechanisms of insulin resistance
Shulman, G. I. (2000) · Journal of Clinical Investigation · doi:10.1172/jci10583 · Cited by 2,714
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
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
Flagged first, then by citations
Cited by
Sorted by citations
DeFronzo, R. A. (2009) · Diabetes · doi:10.2337/db09-9028 · Cited by 3,016
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
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
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
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
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 1,461
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 1,468
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
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
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 1,291
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 1,268
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
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
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
Regulation of mitochondrial biogenesis
Jornayvaz, F. R., & Shulman, G. I. (2010) · Essays in Biochemistry · doi:10.1042/bse0470069 · Cited by 1,119
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
AMP-activated protein kinase signaling in metabolic regulation
Long, Y. C. (2006) · Journal of Clinical Investigation · doi:10.1172/jci29044 · Cited by 1,125
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
Handschin, C., & Spiegelman, B. M. (2006) · Endocrine Reviews · doi:10.1210/er.2006-0037 · Cited by 1,090
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
Copps, K. D., & White, M. F. (2012) · Diabetologia · doi:10.1007/s00125-012-2644-8 · Cited by 1,017
“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
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 888
Morino, K., Petersen, K. F., & Shulman, G. I. (2006) · Diabetes · doi:10.2337/db06-s002 · Cited by 853
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
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
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
Sivitz, W. I., & Yorek, M. A. (2010) · Antioxidants & Redox Signaling · doi:10.1089/ars.2009.2531 · Cited by 742
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
Mechanisms of insulin resistance in obesity
Ye, J. (2013) · Frontiers of Medicine · doi:10.1007/s11684-013-0262-6 · Cited by 699
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
Mitochondrial dysfunction in diabetic kidney disease
Forbes, J. M., & Thorburn, D. R. (2018) · Nature Reviews Nephrology · doi:10.1038/nrneph.2018.9 · Cited by 645
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 693
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
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
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
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 594
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 603
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
Mitochondrial dysfunction and insulin resistance: an update
Montgomery, M. K., & Turner, N. A. (2014) · Endocrine Connections · doi:10.1530/ec-14-0092 · Cited by 549
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
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
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
Diacylglycerol-mediated insulin resistance
Erion, D. M., & Shulman, G. I. (2010) · Nature Medicine · doi:10.1038/nm0410-400 · Cited by 502
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
Current views on type 2 diabetes
Lin, Y., & Sun, Z. (2010) · Journal of Endocrinology · doi:10.1677/joe-09-0260 · Cited by 457
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
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
“These data are consistent with the clinical observations of body weight loss and reduction of food intake in metformin-treated patients with T2D (Adeyemo et al., 2015; Knowler et al., 2002).”
BackgroundInfluentialFiehn, 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 424
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
Villena, J. A. (2014) · FEBS Journal · doi:10.1111/febs.13175 · Cited by 413
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
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 394
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 375
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 373
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
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 369
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
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 364
Fyfe, J. J., Bishop, D. J., & Stepto, N. K. (2014) · Sports Medicine · doi:10.1007/s40279-014-0162-1 · Cited by 347
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
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
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 318
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 331
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
DeFronzo, R. A., & Abdul‐Ghani, M. A. (2011) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2011.03.013 · Cited by 324
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 320
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
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 307
Vanweert, F., Schrauwen, P., & Phielix, E. (2022) · Nutrition and Diabetes · doi:10.1038/s41387-022-00213-3 · Cited by 331
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
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 306
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 297
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 298
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
Corpeleijn, E., Saris, W. H. M., & Blaak, E. E. (2009) · Obesity Reviews · doi:10.1111/j.1467-789x.2008.00544.x · Cited by 280
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
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
“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 274
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 271
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 271
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 276
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 277
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 261
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 267
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 259
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
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 243
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 233
Lepretti, M., Martucciello, S., Burgos Aceves, M., Putti, R., & Lionetti, L. (2018) · Nutrients · doi:10.3390/nu10030350 · Cited by 232
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 224
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 232
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
Regulation of Endothelial Function by Mitochondrial Reactive Oxygen Species
Widlansky, M. E., & Gutterman, D. D. (2011) · Antioxidants and Redox Signaling · doi:10.1089/ars.2010.3642 · Cited by 218
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
Metabolic Complications of Childhood Obesity
Weiss, R., & Kaufman, F. R. (2008) · Diabetes Care · doi:10.2337/dc08-s273 · Cited by 209
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
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
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
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
Metadata
- 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 (medical) › 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
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.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
