Impaired Mitochondrial Substrate Oxidation in Muscle of Insulin-Resistant Offspring of Type 2 Diabetic Patients
Open accessAbstract
Insulin resistance is the best predictor for the development of diabetes in offspring of type 2 diabetic patients, but the mechanism responsible for it remains unknown. Recent studies have demonstrated increased intramyocellular lipid, decreased mitochondrial ATP synthesis, and decreased mitochondrial density in the muscle of lean, insulin-resistant offspring of type 2 diabetic patients. These data suggest an important role for mitochondrial dysfunction in the pathogenesis of type 2 diabetes. To further explore this hypothesis, we assessed rates of substrate oxidation in the muscle of these same individuals using 13C magnetic resonance spectroscopy (MRS). Young, lean, insulin-resistant offspring of type 2 diabetic patients and insulin-sensitive control subjects underwent 13C MRS studies to noninvasively assess rates of substrate oxidation in muscle by monitoring the incorporation of 13C label into C4 glutamate during a [2-13C]acetate infusion. Using this approach, we found that rates of muscle mitochondrial substrate oxidation were decreased by 30% in lean, insulin-resistant offspring (59.8 ± 5.1 nmol · g−1 · min−1, P = 0.02) compared with insulin-sensitive control subjects (96.1 ± 16.3 nmol · g−1 · min−1). These data support the hypothesis that insulin resistance in skeletal muscle of insulin-resistant offspring is associated with dysregulation of intramyocellular fatty acid metabolism, possibly because of an inherited defect in the activity of mitochondrial oxidative phosphorylation.
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Lean normal-glucose-tolerant insulin-resistant offspring of type 2 diabetic parents have a 30-40% decrease in metabolic flux through the tricarboxylic acid cycle and oxidative phosphorylation in skeletal muscle under basal conditions.
“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.”
From Pathogenesis of insulin resistance in skeletal muscle (2010) · cites this paper as [104]
In vivo reports show that incorporation of 13C-acetate into glutamate and mitochondrial phosphorylation is approximately 30% lower in muscle of insulin-resistant versus lean individuals.
“This hypothesis is supported by in vivo reports that the incorporation of 13 C-acetate into glutamate and mitochondrial phosphorylation was approximately 30% lower in muscle of insulin-resistant versus lean individuals (81,83).”
From Altered mitochondrial function in insulin-deficient and insulin-resistant states (2018) · cites this paper as [83]
Multiple mitochondrial abnormalities are present in type 2 diabetic and insulin-resistant individuals.
“These data and the evidence indicating multiple mitochondrial abnormalities in type 2 diabetic and insulin-resistant individuals ([3](#r3), [25](#r25), [36](#r36), [37](#r37), [40](#r40), [42](#r42), [43](#r43), [48](#r48), [59](#r59)) led to the hypothesis that lower mitochondrial capacity is associated with reduced resting lipid oxidation and therefore increased muscle lipid accumulation.”
From Metabolic flexibility and insulin resistance (2008) · cites this paper as [3]
The mitochondrial capacity to oxidize acetyl-CoA coming from glucose is conserved in insulin-resistant subjects even if mitochondrial defects have been reported in those individuals.
“Furthermore, the mitochondrial capacity to oxidize acetyl-CoA coming from glucose is conserved in insulin-resistant subjects even if mitochondrial defects have been reported in those individuals ([3](#r3), [25](#r25), [36](#r36), [37](#r37), [40](#r40), [42](#r42), [43](#r43), [48](#r48), [59](#r59)).”
From Metabolic flexibility and insulin resistance (2008) · cites this paper as [3]
Rates of mitochondrial OXPHOS in offspring of type 2 diabetic subjects, assessed by 31P spectroscopy, are reduced by 30% in the fasting state, and TCA cycle flux is reduced by 30%.
“For example, rates of mitochondrial OXPHOS in offspring of type 2 diabetic subjects, as assessed by 31 P spectroscopy, are reduced by 30% in the fasting state (117), and TCA cycle flux, modeled using rates of 4-13 C-glutamate enrichment during infusion of 13 C-acetate, is reduced by 30% (118).”
From The role of mitochondria in the pathogenesis of type 2 diabetes (2010) · cites this paper as [118]
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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
Wu, Z., Puigserver, P., Andersson, U., Zhang, C., Adelmant, G., Mootha, V., Troy, A., Cinti, S., Lowell, B., Scarpulla, R. C., et al. (1999) · Cell · doi:10.1016/s0092-8674(00)80611-x · Cited by 4,139 · 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
Cellular mechanisms of insulin resistance
Shulman, G. I. (2000) · Journal of Clinical Investigation · doi:10.1172/jci10583 · Cited by 2,714 · see citing works
Self-citationImpaired 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
Self-citationMitochondrial dysfunction in the elderly: possible role in insulin resistance
Petersen, K. F., Befroy, D., Dufour, S., Dziura, J., Ariyan, C., Rothman, D. L., DiPietro, L., Cline, G. W., & Shulman, G. I. (2003) · Science · doi:10.1126/science.1082889 · Cited by 2,107 · see citing works
Self-citationPatti, 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
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
Self-citationItani, 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
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
Self-citationGriffin, 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
Self-citationKrssak, 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
Self-citationDistortionless enhancement of NMR signals by polarization transfer
Doddrell, D. M., Pegg, D. T., & Bendall, M. R. (1982) · Journal of Magnetic Resonance (1969) · doi:10.1016/0022-2364(82)90286-4 · Cited by 1,182 · see citing works
Warram, J. H., Martin, B. C., Krolewski, A. S., Soeldner, J. S., & Kahn, C. R. (1990) · Annals of Internal Medicine · doi:10.7326/0003-4819-113-12-909 · Cited by 1,038 · 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
Morino, K., Petersen, K. F., & Shulman, G. I. (2006) · Diabetes · doi:10.2337/db06-s002 · Cited by 853 · see citing works
Self-citationMorino, K. (2005) · Journal of Clinical Investigation · doi:10.1172/jci25151 · Cited by 811 · 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
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
Self-citationJacob, S., Machann, J., Rett, K., Brechtel, K., Volk, A., Renn, W., Maerker, E., Matthaei, S., Schick, F., Claussen, C. D., et al. (1999) · Diabetes · doi:10.2337/diabetes.48.5.1113 · Cited by 643 · see citing works
Increased prevalence of insulin resistance and nonalcoholic fatty liver disease in Asian-Indian men
Petersen, K. F., Dufour, S., Feng, J., Befroy, D., Dziura, J., Man, C. D., Cobelli, C., & Shulman, G. I. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0608537103 · Cited by 403 · see citing works
Self-citationPhillips, D. I. W., Caddy, S., Ilic, V., Fielding, B. A., Frayn, K. N., Borthwick, A. C., & Taylor, R. (1996) · Metabolism · doi:10.1016/s0026-0495(96)90260-7 · Cited by 390 · see citing works
Metabolic defects in lean nondiabetic offspring of NIDDM parents: a cross-sectional study
Perseghin, G., Ghosh, S., Gerow, K., & Shulman, G. I. (1997) · Diabetes · doi:10.2337/diab.46.6.1001 · Cited by 367 · see citing works
Self-citationPetersen, K. F., Dufour, S., & Shulman, G. I. (2005) · PLoS Medicine · doi:10.1371/journal.pmed.0020233 · Cited by 308 · see citing works
Self-citationEk, J., Andersen, G., Urhammer, S. A., Gæde, P. H., Drivsholm, T., Borch-Johnsen, K., Hansen, T., & Pedersen, O. (2001) · Diabetologia · doi:10.1007/s001250100032 · Cited by 293 · see citing works
NMR Determination of the TCA Cycle Rate and α-Ketoglutarate/Glutamate Exchange Rate in Rat Brain
Mason, G. F., Rothman, D. L., Behar, K. L., & Shulman, R. G. (1992) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.1992.61 · Cited by 249 · see citing works
Self-citationEffect of triiodothyronine on mitochondrial energy coupling in human skeletal muscle
Lebon, V., Dufour, S., Petersen, K. F., Ren, J., Jucker, B. M., Slezak, L. A., Cline, G. W., Rothman, D. L., & Shulman, G. I. (2001) · Journal of Clinical Investigation · doi:10.1172/jci200111775 · Cited by 174 · see citing works
Self-citationEffect of triiodothyronine on mitochondrial energy coupling in human skeletal muscle
Lebon, V., Dufour, S., Petersen, K. F., Ren, J., Jucker, B. M., Slezak, L. A., Cline, G. W., Rothman, D. L., & Shulman, G. I. (2001) · Journal of Clinical Investigation · doi:10.1172/jci11775 · Cited by 173 · see citing works
Self-citationMuller, Y. L., Bogardus, C., Pedersen, O. B., & Baier, L. J. (2003) · Diabetes · doi:10.2337/diabetes.52.3.895 · Cited by 141 · see citing works
Razak, F. A., & Anand, S. S. (2004) · Vascular Medicine · doi:10.1191/1358863x04vm568xx · Cited by 134 · see citing works
Improvements on an in Vivo automatic shimming method (FASTERMAP)
Shen, J., Rycyna, R. E., & Rothman, D. L. (1997) · Magnetic Resonance in Medicine · doi:10.1002/mrm.1910380521 · Cited by 123 · see citing works
Self-citationMetabolic defects in lean nondiabetic offspring of NIDDM parents: a cross-sectional study
Perseghin, G., Ghosh, S., Gerow, K., et al. (1997) · Diabetes · doi:10.2337/diabetes.46.6.1001 · Cited by 118 · see citing works
Assessment of mitochondrial energy coupling in vivo by 13 C/ 31 P NMR
Jucker, B. M., Dufour, S., Ren, J., Cao, X., Previs, S. F., Underhill, B., Cadman, K. S., & Shulman, G. I. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.120131997 · Cited by 99 · see citing works
Self-citationLattuada, G., Costantino, F., Caumo, A., Scifo, P., Ragogna, F., COBELLI, F. D., Maschio, A. D., Luzi, L., & Perseghin, G. (2005) · Diabetologia · doi:10.1007/s00125-005-1686-6 · Cited by 44 · see citing works
Pihlajamäki, J., Alanne-Kinnunen, M., Ruotsalainen, E., Salmenniemi, U., Vauhkonen, I., Kuulasmaa, T., Kainulainen, S., & Laakso, M. (2005) · Diabetologia · doi:10.1007/s00125-005-1800-9 · Cited by 27 · see citing works
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- [23]Mason GF. Cwave software for the design and analysis of 13C labeling studies performed in-vivo (Abstract) Proc Int Soc Magn Reson Med. 2000;3:1870. [Google Scholar]
Cited by
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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
Self-citationThe 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
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
Self-citationEctopic Fat in Insulin Resistance, Dyslipidemia, and Cardiometabolic Disease
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Self-citationDisordered 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
Self-citationRole 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
Metabolic Syndrome and Insulin Resistance: Underlying Causes and Modification by Exercise Training
Roberts, C. K., Hevener, A. L., & Barnard, R. J. (2012) · Comprehensive physiology · doi:10.1002/cphy.c110062 · Cited by 919 · see citing works
Hirschey, M. D., Shimazu, T., Jing, E., Grueter, C. A., Collins, A. M., Aouizerat, B., Stančáková, A., Goetzman, E., Lam, M. M., Schwer, B., et al. (2011) · Molecular Cell · doi:10.1016/j.molcel.2011.07.019 · Cited by 787 · 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
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
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
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
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Golpich, M., Amini, E., Mohamed, Z., Raymond, A. A., Ibrahim, N. M., & Ahmadiani, A. (2016) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.12655 · Cited by 540 · see citing works
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Galgani, J. E., Moro, C., & Ravussin, E. (2008) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90558.2008 · Cited by 532 · see citing works
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Erion, D. M., & Shulman, G. I. (2010) · Nature Medicine · doi:10.1038/nm0410-400 · Cited by 493 · see citing works
Self-citationJing, E., Emanuelli, B., Hirschey, M. D., Boucher, J., Lee, K. Y., Lombard, D., Verdin, E. M., & Kahn, C. R. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1111308108 · Cited by 469 · see citing works
Correa-de-Araujo, R., Addison, O., Miljkovic, I., Goodpaster, B. H., Bergman, B. C., Clark, R. V., Elena, J. W., Esser, K. A., Ferrucci, L., Harris-Love, M. O., et al. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.00963 · Cited by 468 · see citing works
Self-citationFiehn, 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
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
Meex, R. C. R., Schrauwen-Hinderling, V. B., Moonen-Kornips, E., Schaart, G., Mensink, M., Phielix, E., van de Weijer, T., Sels, J.-P., Schrauwen, P., & Hesselink, M. K. C. (2010) · Diabetes · doi:10.2337/db09-1322 · Cited by 355 · 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
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Jornayvaz, F. R., & Shulman, G. I. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.03.005 · Cited by 315 · see citing works
Self-citationDevelopment of insulin resistance in mice lacking PGC-1α in adipose tissues
Kleiner, S., Mepani, R. J., Laznik, D., Li, Y., Jurczak, M. J., Jornayvaz, F. R., Estall, J. L., Bhowmick, D. C., Shulman, G. I., & Spiegelman, B. M. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1207287109 · Cited by 286 · see citing works
Self-citationSirt3 regulates metabolic flexibility of skeletal muscle through reversible enzymatic deacetylation
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Self-citationAguer, C., Gambarotta, D., Mailloux, R. J., Moffat, C., Dent, R., McPherson, R., & Harper, M.-E. (2011) · PLoS ONE · doi:10.1371/journal.pone.0028536 · Cited by 276 · see citing works
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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
Self-citationImpact of short‐term high‐fat feeding on glucose and insulin metabolism in young healthy men
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Hwang, H., Bowen, B. P., Lefort, N., Flynn, C. R., De Filippis, E. A., Roberts, C., Smoke, C. C., Meyer, C., Højlund, K., Yi, Z., et al. (2010) · Diabetes · doi:10.2337/db09-0214 · Cited by 255 · see citing works
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Buch, A., Carmeli, E., Boker, L. K., Marcus, Y., Shefer, G., Kis, O., Berner, Y., & Stern, N. (2016) · Experimental Gerontology · doi:10.1016/j.exger.2016.01.008 · Cited by 227 · see citing works
Roshanravan, B., Gamboa, J. L., & Wilund, K. R. (2017) · American Journal of Kidney Diseases · doi:10.1053/j.ajkd.2017.01.051 · Cited by 227 · see citing works
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Self-citationJacobs, R. A., & Lundby, C. (2013) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01081.2012 · Cited by 222 · see citing works
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Fatty acid metabolism, energy expenditure and insulin resistance in muscle
Turner, N. A., Cooney, G. J., Kraegen, E. W., & Bruce, C. R. (2013) · Journal of Endocrinology · doi:10.1530/joe-13-0397 · Cited by 198 · see citing works
Strength Training as a Countermeasure to Aging Muscle and Chronic Disease
Hurley, B. F., Hanson, E. D., & Sheaff, A. K. (2011) · Sports Medicine · doi:10.2165/11585920-000000000-00000 · Cited by 197 · see citing works
Clark, M. G. (2008) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90477.2008 · Cited by 188 · see citing works
Targeting fatty acid metabolism to improve glucose metabolism
Stinkens, R., Goossens, G. H., Jocken, J. W. E., & Blaak, E. E. (2015) · Obesity Reviews · doi:10.1111/obr.12298 · Cited by 183 · see citing works
SIRT3 regulates mitochondrial protein acetylation and intermediary metabolism
Hirschey, M. D., Shimazu, T., Huang, J. Y., Schwer, B., & Verdin, E. (2011) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2011.76.010850 · Cited by 180 · see citing works
Skeletal muscle “mitochondrial deficiency” does not mediate insulin resistance
Holloszy, J. O. (2009) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.2008.26717c · Cited by 175 · see citing works
Implicating the effect of ketogenic diet as a preventive measure to obesity and diabetes mellitus
Kumar, S., Behl, T., Sachdeva, M., Sehgal, A., Kumari, S., Kumar, A., Kaur, G., Yadav, H. N., & BUNGAU, S. G. (2020) · Life Sciences · doi:10.1016/j.lfs.2020.118661 · Cited by 175 · see citing works
Lefort, N., Glancy, B., Bowen, B., Willis, W. T., Bailowitz, Z., De Filippis, E. A., Brophy, C., Meyer, C., Højlund, K., Yi, Z., et al. (2010) · Diabetes · doi:10.2337/db10-0174 · Cited by 174 · see citing works
Hsu, Y.-Y., Chen, C., Wu, S., Jong, Y., & Lo, Y. (2012) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2012.03.004 · Cited by 165 · see citing works
Methods for Assessing Mitochondrial Function in Diabetes
Perry, C. G. R., Kane, D. A., Lanza, I. R., & Neufer, P. D. (2013) · Diabetes · doi:10.2337/db12-1219 · Cited by 165 · see citing works
Is mitochondrial dysfunction a cause of insulin resistance?
Turner, N. A., & Heilbronn, L. K. (2008) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2008.08.001 · Cited by 163 · see citing works
Hidalgo, B., Irvin, M. R., Sha, J., Zhi, D., Aslibekyan, S., Absher, D., Tiwari, H. K., Kabagambe, E. K., Ordovas, J. M., & Arnett, D. K. (2014) · Diabetes · doi:10.2337/db13-1100 · Cited by 160 · see citing works
Kemp, G. J., Ahmad, R., Nicolay, K., & Prompers, J. J. (2014) · Acta Physiologica · doi:10.1111/apha.12307 · Cited by 158 · see citing works
Eckardt, K., Taube, A., & Eckel, J. (2011) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-011-9168-2 · Cited by 157 · see citing works
The Role of Mitochondria in the Pathophysiology of Skeletal Muscle Insulin Resistance
Pagel-Langenickel, I., Bao, J., Pang, L., & Sack, M. N. (2010) · Endocrine Reviews · doi:10.1210/er.2009-0003 · Cited by 154 · see citing works
Insulin Resistance and Mitochondrial Dysfunction
González-Franquesa, A., & Patti, M. (2017) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-55330-6_25 · Cited by 154 · see citing works
Cardiometabolic characteristics of people with metabolically healthy and unhealthy obesity
Petersen, M. C., Smith, G. I., Palacios, H. H., Farabi, S. S., Yoshino, M., Yoshino, J., Cho, K., Davila-Roman, V. G., Shankaran, M., Barve, R. A., et al. (2024) · Cell Metabolism · doi:10.1016/j.cmet.2024.03.002 · Cited by 149 · see citing works
Self-citationMitochondrial dysfunction, insulin resistance, and type 2 diabetes mellitus
Abdul-Ghani, M. A., & DeFronzo, R. A. (2008) · Current Diabetes Reports · doi:10.1007/s11892-008-0030-1 · Cited by 146 · see citing works
Type 2 diabetes mellitus and exercise impairment
Reusch, J. E. B., Bridenstine, M., & Regensteiner, J. G. (2013) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-012-9234-4 · Cited by 137 · see citing works
Mitochondrial Dysfunction in Type 2 Diabetes and Obesity
Højlund, K., Mogensen, M., Sahlin, K., & Beck-Nielsen, H. (2008) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2008.06.006 · Cited by 135 · see citing works
Strasser, B., & Pesta, D. H. (2013) · BioMed Research International · doi:10.1155/2013/805217 · Cited by 125 · see citing works
Review: Quantifying Mitochondrial Dysfunction in Complex Diseases of Aging
Horan, M. P., Pichaud, N., & Ballard, J. W. O. (2012) · The Journals of Gerontology Series A · doi:10.1093/gerona/glr263 · Cited by 125 · see citing works
Pagel-Langenickel, I., Bao, J., Joseph, J. J., Schwartz, D. R., Mantell, B. S., Xu, X., Raghavachari, N., & Sack, M. N. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m800842200 · Cited by 124 · see citing works
Sparks, L. M., Johannsen, N. M., Church, T. S., Earnest, C. P., Moonen-Kornips, E., Moro, C., Hesselink, M. K. C., Smith, S. R., & Schrauwen, P. (2013) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2012-3874 · Cited by 123 · see citing works
Axelrod, C. L., Fealy, C. E., Mulya, A., & Kirwan, J. P. (2018) · Acta Physiologica · doi:10.1111/apha.13216 · Cited by 120 · see citing works
Resistance training, visceral obesity and inflammatory response: a review of the evidence
Strasser, B., Arvandi, M., & Siebert, U. (2012) · Obesity Reviews · doi:10.1111/j.1467-789x.2012.00988.x · Cited by 120 · see citing works
Befroy, D. E., Petersen, K. F., Dufour, S., Mason, G. F., Rothman, D. L., & Shulman, G. I. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0808889105 · Cited by 118 · see citing works
Self-citationMetabolomics – the complementary field in systems biology: a review on obesity and type 2 diabetes
Bakar, M. H. A., Sarmidi, M. R., Cheng, K., Khan, A. A., Suan, C. L., Huri, H. Z., & Yaakob, H. (2015) · Molecular BioSystems · doi:10.1039/c5mb00158g · Cited by 117 · see citing works
Mitchell, C. S., Savage, D. B., Dufour, S., Schoenmakers, N. A., Murgatroyd, P. R., Befroy, D. E., Halsall, D. J., Northcott, S., Raymond‐Barker, P., Curran, S., et al. (2010) · Journal of Clinical Investigation · doi:10.1172/jci38793 · Cited by 115 · see citing works
Self-citationImpaired estrogen receptor action in the pathogenesis of the metabolic syndrome
Hevener, A. L., Clegg, D. J., & Mauvais-Jarvis, F. (2015) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2015.05.020 · Cited by 112 · see citing works
“Deficiency” of Mitochondria in Muscle Does Not Cause Insulin Resistance
Holloszy, J. O. (2013) · Diabetes · doi:10.2337/db12-1107 · Cited by 111 · see citing works
Adipose Tissue in Metabolic Syndrome: Onset and Progression of Atherosclerosis
Luna‐Luna, M., Medina-Urrutia, A. X., Vargas‐Alarcón, G., Coss-Rovirosa, F., Vargas‐Barrón, J., & Pérez-Méndez, O. A. (2015) · Archives of Medical Research · doi:10.1016/j.arcmed.2015.05.007 · Cited by 111 · see citing works
Yan, J., Feng, Z., Liu, J., Shen, W., Wang, Y., Wertz, K., Weber, P., Long, J., & Liu, J. (2012) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2011.03.014 · Cited by 110 · see citing works
Aguer, C., Mercier, J. G., Man, C. Y. W., Metz, L., Bordenave, S., Lambert, K., Jean, E., Lantier, L., Bounoua, L., Brun, J. ‐., et al. (2010) · Diabetologia · doi:10.1007/s00125-010-1708-x · Cited by 110 · see citing works
Brøns, C., & Grunnet, L. G. (2016) · European Journal of Endocrinology · doi:10.1530/eje-16-0488 · Cited by 109 · see citing works
Altered lipid metabolism in a Drosophila model of Friedreich's ataxia
Navarro, J. A., Ohmann, E., Sánchez, D., Botella, J., Liebisch, G., Moltó, M. D., Ganfornina, M. D., Schmitz, G., & Schneuwly, S. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq183 · Cited by 106 · see citing works
Civitarese, A. E., MacLean, P. S., Carling, S., Kerr-Bayles, L., McMillan, R. P., Pierce, A., Becker, T. C., Moro, C., Finlayson, J., Lefort, N., et al. (2010) · Cell Metabolism · doi:10.1016/j.cmet.2010.04.004 · Cited by 95 · see citing works
Befroy, D. E., Perry, R. J., Jain, N., Dufour, S., Cline, G. W., Trimmer, J. K., Brosnan, J. M., Rothman, D. L., Petersen, K. F., & Shulman, G. I. (2013) · Nature Medicine · doi:10.1038/nm.3415 · Cited by 95 · see citing works
Self-citationMuscle mitochondria and insulin resistance: a human perspective
Hoeks, J., & Schrauwen, P. (2012) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2012.05.007 · Cited by 94 · see citing works
Qiao, L., Kinney, B., Yoo, H. S., Lee, B., Schaack, J. B., & Shao, J. (2012) · Diabetes · doi:10.2337/db11-1475 · Cited by 94 · see citing works
Petersen, K. F., Dufour, S., Morino, K., Yoo, P. S., Cline, G. W., & Shulman, G. I. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1205675109 · Cited by 91 · see citing works
Self-citationMitochondria and Diabetes. An Intriguing Pathogenetic Role
Newsholme, P., Gaudel, C., & Krause, M. (2011) · Advances in experimental medicine and biology · doi:10.1007/978-94-007-2869-1_10 · Cited by 90 · see citing works
Pathophysiological role of metabolic flexibility on metabolic health
Galgani, J. E., & Fernández‐Verdejo, R. (2020) · Obesity Reviews · doi:10.1111/obr.13131 · Cited by 90 · see citing works
Hirahatake, K. M., Slavin, J. L., Maki, K. C., & Adams, S. H. (2014) · Metabolism · doi:10.1016/j.metabol.2014.02.009 · Cited by 87 · see citing works
Liu, Y., Gu, Y., & Yu, X. (2017) · Quantitative Imaging in Medicine and Surgery · doi:10.21037/qims.2017.11.03 · Cited by 85 · see citing works
Exogenous H2S Promoted USP8 Sulfhydration to Regulate Mitophagy in the Hearts of db/db Mice
Sun, Y., Lu, F., Yu, X., Wang, B., Chen, J., Lu, F., Peng, S., Sun, X., Yu, M., Chen, H., et al. (2020) · Aging and Disease · doi:10.14336/ad.2019.0524 · Cited by 83 · see citing works
Mitochondrial Dysfunction in Obesity and Reproduction
Das, M., Sauceda, C., & Webster, N. J. G. (2020) · Endocrinology · doi:10.1210/endocr/bqaa158 · Cited by 83 · see citing works
Pyridine Nucleotide Redox Abnormalities in Diabetes
Ido, Y. (2007) · Antioxidants and Redox Signaling · doi:10.1089/ars.2007.1630 · Cited by 83 · see citing works
Brugnara, L., Vinaixa, M., Murillo, S., Samino, S., Rodriguez, M. A., Beltran, A., Lerín, C., Davison, G. W., Correig, X., & Novials, A. (2012) · PLoS ONE · doi:10.1371/journal.pone.0040600 · Cited by 81 · see citing works
The Cardiovascular Risk of Healthy Individuals Studied by NMR Metabonomics of Plasma Samples
Bernini, P., Bertini, I., Luchinat, C., Tenori, L., & Tognaccini, A. (2011) · Journal of Proteome Research · doi:10.1021/pr200452j · Cited by 80 · see citing works
Girard, J. R., & Lafontan, M. (2008) · Diabetes & Metabolism · doi:10.1016/j.diabet.2008.04.002 · Cited by 79 · see citing works
Use of dicarboxylic acids in type 2 diabetes
Mingrone, G., Castagneto‐Gissey, L., & Macé, K. (2012) · British Journal of Clinical Pharmacology · doi:10.1111/j.1365-2125.2012.04177.x · Cited by 78 · see citing works
Diabetes and Alzheimer’s Disease: Might Mitochondrial Dysfunction Help Deciphering the Common Path?
Potenza, M. A., Sgarra, L., Desantis, V., Nacci, C., & Montagnani, M. (2021) · Antioxidants · doi:10.3390/antiox10081257 · Cited by 77 · see citing works
Morino, K., Petersen, K. F., Sono, S., Choi, C. S., Samuel, V. T., Lin, A., Gallo, A. E., Zhao, H., Kashiwagi, A., Goldberg, I. J., et al. (2012) · Diabetes · doi:10.2337/db11-1391 · Cited by 77 · see citing works
Self-citation
- Authors
- Befroy, D. E., Petersen, K. F., Dufour, S., Mason, G. F., de Graaf, R. A., Rothman, D. L., & Shulman, G. I.
- Affiliations
- Yale University (US)
- Howard Hughes Medical Institute (US)
- Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, Connecticut
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2007-05-01
- Volume
- 56
- Issue
- 5
- Pages
- 1376-1381
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- PMC
- PMC2995532
- OpenAlex
- W2152386173
- Cited by
- 453
- References
- 34
- Citations by year
- 2026: 5 · 2025: 15 · 2024: 13 · 2023: 17 · 2022: 14 · 2021: 21 · 2020: 22 · 2019: 14 · 2018: 18 · 2017: 19 · 2016: 24 · 2015: 19 · 2014: 28 · 2013: 34 · 2012: 36
- FWCI
- 15.75
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (R56AG023686, R01AG023686)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK049230, P30DK045735, P01DK068229)
- National Center for Research Resources (M01RR000125)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- insulin resistance, type 2 diabetes, offspring of diabetic patients, skeletal muscle, fatty acid oxidation, intramyocellular lipid, oxidative phosphorylation, 13C NMR, glutamate, mitochondrial dysfunction
- MeSH terms
- Adult, Carbon Isotopes, Citric Acid Cycle, Diabetes Mellitus, Type 2, Female, Glucose Tolerance Test, Humans, Insulin Resistance, Kinetics, Life Style, Male, Mitochondria, Muscle, Models, Biological, Nuclear Family, Magnetic Resonance Spectroscopy, Oxidation-Reduction, Body Mass Index
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