{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T19:18:28Z","timestamp":1790363908181,"version":"4.1.0"},"reference-count":138,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2019,6,5]],"date-time":"2019-06-05T00:00:00Z","timestamp":1559692800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000291","name":"Kidney Research UK","doi-asserted-by":"publisher","award":["Daphne Jackon Fellowship"],"award-info":[{"award-number":["Daphne Jackon Fellowship"]}],"id":[{"id":"10.13039\/501100000291","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Insulin resistance is a key feature of the metabolic syndrome, a cluster of medical disorders that together increase the chance of developing type 2 diabetes and cardiovascular disease. In turn, type 2 diabetes may cause complications such as diabetic kidney disease (DKD). Obesity is a major risk factor for developing systemic insulin resistance, and skeletal muscle is the first tissue in susceptible individuals to lose its insulin responsiveness. Interestingly, lean individuals are not immune to insulin resistance either. Non-obese, non-diabetic subjects with chronic kidney disease (CKD), for example, exhibit insulin resistance at the very onset of CKD, even before clinical symptoms of renal failure are clear. This uraemic insulin resistance contributes to the muscle weakness and muscle wasting that many CKD patients face, especially during the later stages of the disease. Bioenergetic failure has been associated with the loss of skeletal muscle insulin sensitivity in obesity and uraemia, as well as in the development of kidney disease and its sarcopenic complications. In this mini review, we evaluate how mitochondrial activity of different renal cell types changes during DKD progression, and discuss the controversial role of oxidative stress and mitochondrial reactive oxygen species in DKD. We also compare the involvement of skeletal muscle mitochondria in uraemic and obesity-related muscle insulin resistance.<\/jats:p>","DOI":"10.3390\/ijms20112751","type":"journal-article","created":{"date-parts":[[2019,6,5]],"date-time":"2019-06-05T09:37:58Z","timestamp":1559727478000},"page":"2751","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Mitochondrial Activity and Skeletal Muscle Insulin Resistance in Kidney Disease"],"prefix":"10.3390","volume":"20","author":[{"given":"Jane E.","family":"Carr\u00e9","sequence":"first","affiliation":[{"name":"School of Biomedical Sciences, University of Plymouth, Plymouth PL6 8BU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1776-9943","authenticated-orcid":false,"given":"Charles","family":"Affourtit","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, University of Plymouth, Plymouth PL6 8BU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,6,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1152\/physrev.00008.2017","article-title":"Pancreatic \u03b2-cell electrical activity and insulin secretion: Of mice and men","volume":"98","author":"Rorsman","year":"2018","journal-title":"Physiol. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2133","DOI":"10.1152\/physrev.00063.2017","article-title":"Mechanisms of insulin action and insulin resistance","volume":"98","author":"Petersen","year":"2018","journal-title":"Physiol. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1210\/edrv.19.4.0336","article-title":"Insulin resistance versus insulin deficiency in non-insulin-dependent diabetes mellitus: Problems and prospects","volume":"19","author":"Ferrannini","year":"1998","journal-title":"Endocr. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1146\/annurev.biochem.75.103004.142622","article-title":"Signaling pathways in skeletal muscle remodeling","volume":"75","author":"Olson","year":"2006","journal-title":"Annu. Rev. Biochem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1038\/nrneph.2014.112","article-title":"Mechanisms of muscle wasting in chronic kidney disease","volume":"10","author":"Wang","year":"2014","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"44","DOI":"10.3389\/fphys.2016.00361","article-title":"Human skeletal muscle disuse atrophy: Effects on muscle protein synthesis, breakdown, and insulin resistance\u2014A qualitative review","volume":"7","author":"Rudrappa","year":"2016","journal-title":"Front. Physiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1016\/j.tem.2010.06.005","article-title":"Insulin signaling meets mitochondria in metabolism","volume":"21","author":"Cheng","year":"2010","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1038\/nm.4350","article-title":"Insulin action and resistance in obesity and type 2 diabetes","volume":"23","author":"Czech","year":"2017","journal-title":"Nat. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"109","DOI":"10.4239\/wjd.v6.i1.109","article-title":"\u03b2-cell dysfunction: Its critical role in prevention and management of type 2 diabetes","volume":"6","author":"Saisho","year":"2015","journal-title":"World J. Diabetes"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3086167","DOI":"10.1155\/2018\/3086167","article-title":"Complications of diabetes 2017","volume":"2018","author":"Papatheodorou","year":"2018","journal-title":"J. Diabetes Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"15018","DOI":"10.1038\/nrdp.2015.18","article-title":"Diabetic kidney disease","volume":"1","author":"Thomas","year":"2015","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.metabol.2018.09.005","article-title":"The epidemiology of obesity","volume":"92","author":"Chooi","year":"2019","journal-title":"Metab. Clin. Exp."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1038\/nrendo.2017.151","article-title":"Global aetiology and epidemiology of type 2 diabetes mellitus and its complications","volume":"14","author":"Zheng","year":"2018","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"(2018). Professional Practice Committee: Standards of Medical Care in Diabetes-2018. Diabetes Care, 41, S3.","DOI":"10.2337\/dc18-Sppc01"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1038\/nrm1837","article-title":"Critical nodes in signalling pathways: Insights into insulin action","volume":"7","author":"Taniguchi","year":"2006","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1678","DOI":"10.1016\/j.bbabio.2016.07.008","article-title":"Mitochondrial involvement in skeletal muscle insulin resistance: A case of imbalanced bioenergetics","volume":"1857","author":"Affourtit","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_17","first-page":"F1087","article-title":"Insulin resistance in chronic kidney disease: A systematic review","volume":"311","author":"Spoto","year":"2016","journal-title":"Am. J. Physiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1097\/MNH.0000000000000318","article-title":"Clinical relevance of sarcopenia in chronic kidney disease","volume":"26","author":"Moorthi","year":"2017","journal-title":"Curr. Opin. Nephrol. Hypertens."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Hill, N.R., Fatoba, S.T., Oke, J.L., Hirst, J.A., O\u2019Callaghan, C.A., Lasserson, D.S., and Hobbs, F.D.R. (2016). Global prevalence of chronic kidney disease\u2014A systematic review and meta-analysis. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0158765"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1097\/MNH.0000000000000393","article-title":"Chronic kidney disease and acquired mitochondrial myopathy","volume":"27","author":"Rao","year":"2018","journal-title":"Curr. Opin. Nephrol. Hypertens."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.cmet.2010.08.015","article-title":"Insulin signaling to the glomerular podocyte is critical for normal kidney function","volume":"12","author":"Welsh","year":"2010","journal-title":"Cell Metab."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"85","DOI":"10.3389\/fendo.2018.00693","article-title":"The evolving importance of insulin signaling in podocyte health and disease","volume":"9","author":"Lay","year":"2018","journal-title":"Front. Endocrinol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1038\/nrneph.2018.9","article-title":"Mitochondrial dysfunction in diabetic kidney disease","volume":"14","author":"Forbes","year":"2018","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1038\/s41581-018-0051-1","article-title":"Metabolism and mitochondria in polycystic kidney disease research and therapy","volume":"14","author":"Padovano","year":"2018","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/j.cmet.2013.03.002","article-title":"Mitochondrial dynamics in the regulation of nutrient utilization and energy expenditure","volume":"17","author":"Liesa","year":"2013","journal-title":"Cell Metab."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1038\/nrneph.2017.107","article-title":"Mitochondrial energetics in the kidney","volume":"13","author":"Bhargava","year":"2017","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2509","DOI":"10.3389\/fphys.2015.00422","article-title":"Mitochondrial quality control and muscle mass maintenance","volume":"6","author":"Romanello","year":"2016","journal-title":"Front. Physiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"24","DOI":"10.2337\/dc13-2113","article-title":"Kidney disease and related findings in the diabetes control and complications trial\/epidemiology of diabetes interventions and complications study","volume":"37","year":"2014","journal-title":"Diabetes Care"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"ADVANCE Collaborative Group, Patel, A., MacMahon, S., Chalmers, J., Neal, B., Billot, L., Woodward, M., Marre, M., Cooper, M., and Glasziou, P. (2008). Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N. Engl. J. Med., 358, 2560\u20132572.","DOI":"10.1056\/NEJMoa0802987"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Xu, H., Li, X., Adams, H., Kubena, K., and Guo, S. (2018). Etiology of metabolic syndrome and dietary intervention. Int. J. Sport Nutr. Exerc. Metab., 20.","DOI":"10.3390\/ijms20010128"},{"key":"ref_31","unstructured":"Sherwood, L. (2012). Introduction to Human Physiology, Brooks\/Cole, Cengage Learning."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.3945\/ajcn.2010.29885","article-title":"Specific metabolic rates of major organs and tissues across adulthood: Evaluation by mechanistic model of resting energy expenditure","volume":"92","author":"Wang","year":"2010","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"64","DOI":"10.2337\/diab.32.2.S64","article-title":"The stages in diabetic renal disease with emphasis on the stage of incipient diabetic nephropathy","volume":"32","author":"Mogensen","year":"1983","journal-title":"Diabetes"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2032","DOI":"10.2215\/CJN.11491116","article-title":"Diabetic kidney disease: Challenges, progress, and possibilities","volume":"12","author":"Alicic","year":"2017","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1146\/annurev.ph.48.030186.000301","article-title":"ATP and the regulation of renal cell function","volume":"48","author":"Soltoff","year":"1986","journal-title":"Annu. Rev. Physiol."},{"key":"ref_36","first-page":"F357","article-title":"Stoichiometry and coupling of active transport to oxidative metabolism in epithelial tissues","volume":"240","author":"Mandel","year":"1981","journal-title":"Am. J. Physiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.ebiom.2016.03.033","article-title":"Mass spectrometry imaging reveals elevated glomerular ATP\/AMP in diabetes\/obesity and identifies sphingomyelin as a possible mediator","volume":"7","author":"Miyamoto","year":"2016","journal-title":"EBioMedicine"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.semnephrol.2018.01.002","article-title":"The Warburg effect in diabetic kidney disease","volume":"38","author":"Zhang","year":"2018","journal-title":"Semin. Nephrol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1111\/1440-1681.12034","article-title":"Determinants of kidney oxygen consumption and their relationship to tissue oxygen tension in diabetes and hypertension","volume":"40","author":"Hansell","year":"2013","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1016\/j.metabol.2011.12.003","article-title":"Impact of high glucose and transforming growth factor\u2013\u03b2 on bioenergetic profiles in podocytes","volume":"61","author":"Stieger","year":"2012","journal-title":"Metabolism"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1016\/j.bbabio.2008.03.030","article-title":"Diabetes-induced up-regulation of uncoupling protein-2 results in increased mitochondrial uncoupling in kidney proximal tubular cells","volume":"1777","author":"Friederich","year":"2008","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Friederich-Persson, M., Aslam, S., Nordquist, L., Welch, W.J., Wilcox, C.S., and Palm, F. (2012). Acute knockdown of uncoupling protein-2 increases uncoupling via the adenine nucleotide transporter and decreases oxidative stress in diabetic kidneys. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0039635"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1073\/pnas.1317400111","article-title":"UCP2 transports C4 metabolites out of mitochondria, regulating glucose and glutamine oxidation","volume":"111","author":"Vozza","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Qiu, W., Zhou, Y., Jiang, L., Fang, L., Chen, L., Su, W., Tan, R., Zhang, C.-Y., Han, X., and Yang, J. (2012). Genipin inhibits mitochondrial uncoupling protein 2 expression and ameliorates podocyte injury in diabetic mice. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0041391"},{"key":"ref_45","first-page":"F926","article-title":"UCP2 attenuates apoptosis of tubular epithelial cells in renal ischemia-reperfusion injury","volume":"313","author":"Zhou","year":"2017","journal-title":"Am. J. Physiol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"De Souza, B.M., Michels, M., Sortica, D.A., Bou\u00e7as, A.P., Rheinheimer, J., Buffon, M.P., Bauer, A.C., Canani, L.H., and Crispim, D. (2015). Polymorphisms of the UCP2 gene are associated with glomerular filtration rate in type 2 diabetic patients and with decreased UCP2 gene expression in human kidney. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0132938"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1042\/CS20150838","article-title":"Mapping time-course mitochondrial adaptations in the kidney in experimental diabetes","volume":"130","author":"Coughlan","year":"2016","journal-title":"Clin. Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"4888","DOI":"10.1172\/JCI66218","article-title":"AMPK dysregulation promotes diabetes-related reduction of superoxide and mitochondrial function","volume":"123","author":"Dugan","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1038\/nm.3762","article-title":"Defective fatty acid oxidation in renal tubular epithelial cells has a key role in kidney fibrosis development","volume":"21","author":"Kang","year":"2014","journal-title":"Nat. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/j.ebiom.2015.04.002","article-title":"Altered mitochondrial function, mitochondrial DNA and reduced metabolic flexibility in patients with diabetic nephropathy","volume":"2","author":"Czajka","year":"2015","journal-title":"EBioMedicine"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.redox.2016.09.007","article-title":"Hyperglycemia induced damage to mitochondrial respiration in renal mesangial and tubular cells: Implications for diabetic nephropathy","volume":"10","author":"Czajka","year":"2016","journal-title":"Redox Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/BJ20081386","article-title":"How mitochondria produce reactive oxygen species","volume":"417","author":"Murphy","year":"2009","journal-title":"Biochem. J."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.freeradbiomed.2016.04.001","article-title":"Mitochondrial generation of superoxide and hydrogen peroxide as the source of mitochondrial redox signaling","volume":"100","author":"Brand","year":"2016","journal-title":"Free Radic. Biol. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.tips.2010.11.006","article-title":"Reactive oxygen species and insulin resistance: The good, the bad and the ugly","volume":"32","author":"Tiganis","year":"2011","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"405","DOI":"10.2337\/diab.40.4.405","article-title":"Role of oxidative stress in development of complications in diabetes","volume":"40","author":"Baynes","year":"1991","journal-title":"Diabetes"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1038\/414813a","article-title":"Biochemistry and molecular cell biology of diabetic complications","volume":"414","author":"Brownlee","year":"2001","journal-title":"Nature"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1615","DOI":"10.2337\/diabetes.54.6.1615","article-title":"The pathobiology of diabetic complications: A unifying mechanism","volume":"54","author":"Brownlee","year":"2005","journal-title":"Diabetes"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.kint.2016.02.043","article-title":"Challenging the dogma of mitochondrial reactive oxygen species overproduction in diabetic kidney disease","volume":"90","author":"Coughlan","year":"2016","journal-title":"Kidney Int."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1016\/j.freeradbiomed.2018.06.042","article-title":"Nox4 in renal diseases: An update","volume":"124","author":"Yang","year":"2018","journal-title":"Free Radic. Biol. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.freeradbiomed.2018.09.030","article-title":"Indicator of RNA oxidation in urine for the prediction of mortality in patients with type 2 diabetes and microalbuminuria: A post-hoc analysis of the Steno-2 trial","volume":"129","author":"Kjaer","year":"2018","journal-title":"Free Radic. Biol. Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1007\/s00125-017-4510-1","article-title":"Plasma concentrations of 8-hydroxy-2\u2032-deoxyguanosine and risk of kidney disease and death in individuals with type 1 diabetes","volume":"61","author":"Sanchez","year":"2018","journal-title":"Diabetologia"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e245","DOI":"10.1038\/emm.2016.81","article-title":"Regulation and function of AMPK in physiology and diseases","volume":"48","author":"Jeon","year":"2016","journal-title":"Exp. Mol. Med."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Bolignano, D., Cernaro, V., Gembillo, G., Baggetta, R., Buemi, M., and D\u2019Arrigo, G. (2017). Antioxidant agents for delaying diabetic kidney disease progression: A systematic review and meta-analysis. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0178699"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.cbi.2017.10.031","article-title":"Antioxidant for treatment of diabetic nephropathy: A systematic review and meta-analysis","volume":"278","author":"Kandhare","year":"2017","journal-title":"Chemico-Biol. Interact."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1159\/000327599","article-title":"Effect of bardoxolone methyl on kidney function in patients with T2D and Stage 3b-4 CKD","volume":"33","author":"Pergola","year":"2011","journal-title":"Am. J. Nephrol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2492","DOI":"10.1056\/NEJMoa1306033","article-title":"Bardoxolone methyl in type 2 diabetes and stage 4 chronic kidney disease","volume":"369","author":"Akizawa","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"15190","DOI":"10.1038\/s41598-017-15589-x","article-title":"Targeted mitochondrial therapy using MitoQ shows equivalent renoprotection to angiotensin converting enzyme inhibition but no combined synergy in diabetes","volume":"7","author":"Ward","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"3095","DOI":"10.2337\/diabetes.54.11.3095","article-title":"The human glomerular podocyte is a novel target for insulin action","volume":"54","author":"Coward","year":"2005","journal-title":"Diabetes"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"663","DOI":"10.2337\/db14-0874","article-title":"Mitochondrial hormesis and diabetic complications","volume":"64","author":"Sharma","year":"2015","journal-title":"Diabetes"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1016\/j.cmet.2014.01.011","article-title":"Mitohormesis","volume":"19","author":"Yun","year":"2014","journal-title":"Cell Metab."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"8665","DOI":"10.1073\/pnas.0903485106","article-title":"Antioxidants prevent health-promoting effects of physical exercise in humans","volume":"106","author":"Ristow","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.2337\/db12-1612","article-title":"Mitochondrial deficiency is associated with insulin resistance","volume":"62","author":"Goodpaster","year":"2013","journal-title":"Diabetes"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.2337\/db12-1107","article-title":"\u201cDeficiency\u201d of mitochondria in muscle does not cause insulin resistance","volume":"62","author":"Holloszy","year":"2013","journal-title":"Diabetes"},{"key":"ref_74","unstructured":"Jana, B.A. (2018). Cytosolic lipid excess-induced mitochondrial dysfunction is the cause or effect of high fat diet-induced skeletal muscle insulin resistance: A molecular insight. Mol. Biol. Rep."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2457","DOI":"10.1172\/JCI46405","article-title":"Mitochondrial dysfunction in patients with primary congenital insulin resistance","volume":"121","author":"Sleigh","year":"2011","journal-title":"J. Clin. Investig."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1016\/j.cmet.2012.04.010","article-title":"Lipid-induced mitochondrial stress and insulin action in muscle","volume":"15","author":"Muoio","year":"2012","journal-title":"Cell Metab."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1042\/bj3120163","article-title":"A hierarchy of ATP-consuming processes in mammalian cells","volume":"312","author":"Buttgereit","year":"1995","journal-title":"Biochem. J."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1016\/j.bbabio.2016.04.286","article-title":"Palmitate-induced changes in energy demand cause reallocation of ATP supply in rat and human skeletal muscle cells","volume":"1857","author":"Nisr","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1172\/JCI109144","article-title":"Glucose intolerance in uremia. Quantification of pancreatic beta cell sensitivity to glucose and tissue sensitivity to insulin","volume":"62","author":"DeFronzo","year":"1978","journal-title":"J. Clin. Investig."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1172\/JCI110067","article-title":"Insulin resistance in uremia","volume":"67","author":"DeFronzo","year":"1981","journal-title":"J. Clin. Investig."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1046\/j.1523-1755.1998.00898.x","article-title":"Insulin resistance and hyperinsulinemia are already present in patients with incipient renal disease","volume":"53","author":"Fliser","year":"1998","journal-title":"Kidney Int."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"638","DOI":"10.2215\/CJN.01290214","article-title":"Insulin resistance in CKD","volume":"9","author":"Leyking","year":"2014","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_83","first-page":"E394","article-title":"Insulin resistance in uremia: Insulin receptor kinase activity in liver and muscle from chronic uremic rats","volume":"254","author":"Cecchin","year":"1988","journal-title":"Am. J. Physiol."},{"key":"ref_84","first-page":"E87","article-title":"Muscle insulin resistance in uremic humans: Glucose transport, glucose transporters, and insulin receptors","volume":"261","author":"Friedman","year":"1991","journal-title":"Am. J. Physiol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.1681\/ASN.2004100842","article-title":"Chronic kidney disease causes defects in signaling through the insulin receptor substrate\/phosphatidylinositol 3-kinase\/Akt pathway: Implications for muscle atrophy","volume":"17","author":"Bailey","year":"2006","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Bailey, J.L. (2013). Insulin resistance and muscle metabolism in chronic kidney disease. ISRN Endocrinol., 2013.","DOI":"10.1155\/2013\/329606"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1053\/jren.2003.50022","article-title":"Body composition analysis by bioelectrical impedance in chronic maintenance dialysis patients: Comparisons to the National Health and Nutrition Examination Survey III","volume":"13","author":"Dumler","year":"2003","journal-title":"J. Ren. Nutr."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1046\/j.1523-1755.2002.00116.x","article-title":"Lipoprotein particle abnormalities and the impaired lipolysis in renal insufficiency","volume":"61","author":"Lee","year":"2002","journal-title":"Kidney Int."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1093\/ndt\/gfx052","article-title":"Inflamed fat and mitochondrial dysfunction in end-stage renal disease links to hypoxia-could curcumin be of benefit?","volume":"32","author":"Stenvinkel","year":"2017","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1093\/ndt\/gfx050","article-title":"Uremia induces adipose tissue inflammation and muscle mitochondrial dysfunction","volume":"32","author":"Lin","year":"2017","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1111\/j.1523-1755.2004.00465.x","article-title":"Increased prevalence of oxidant stress and inflammation in patients with moderate to severe chronic kidney disease","volume":"65","author":"Oberg","year":"2004","journal-title":"Kidney Int."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/j.semnephrol.2004.06.026","article-title":"Oxidative stress in uremia: Nature, mechanisms, and potential consequences","volume":"24","author":"Vaziri","year":"2004","journal-title":"Semin. Nephrol."},{"key":"ref_93","first-page":"F700","article-title":"Acidosis impairs insulin receptor substrate-1-associated phosphoinositide 3-kinase signaling in muscle cells: Consequences on proteolysis","volume":"287","author":"Franch","year":"2004","journal-title":"Am. J. Physiol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1053\/j.ajkd.2004.09.034","article-title":"Insulin resistance in patients with chronic kidney disease","volume":"45","author":"Kobayashi","year":"2005","journal-title":"Am. J. Kidney Dis."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1007\/s11892-018-1064-7","article-title":"Metabolic abnormalities in diabetes and kidney disease: Role of uremic toxins","volume":"18","author":"Koppe","year":"2018","journal-title":"Curr. Diab. Rep."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Liu, W.C., Tomino, Y., and Lu, K.C. (2018). Impacts of indoxyl sulfate and p-cresol sulfate on chronic kidney disease and mitigating effects of AST-120. Toxins, 10.","DOI":"10.3390\/toxins10090367"},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Vanholder, R., Pletinck, A., Schepers, E., and Glorieux, G. (2018). Biochemical and clinical impact of organic uremic retention solutes: A comprehensive update. Toxins, 10.","DOI":"10.3390\/toxins10010033"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1681\/ASN.2012050503","article-title":"p-Cresyl sulfate promotes insulin resistance associated with CKD","volume":"24","author":"Koppe","year":"2013","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1666","DOI":"10.1093\/ndt\/gft435","article-title":"Insulin resistance in chronic kidney disease: New lessons from experimental models","volume":"29","author":"Koppe","year":"2014","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"30","DOI":"10.2215\/CJN.05340610","article-title":"Indoxyl sulfate-induced endothelial dysfunction in patients with chronic kidney disease via an induction of oxidative stress","volume":"6","author":"Yu","year":"2011","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_101","unstructured":"Sato, E., Mori, T., Mishima, E., Suzuki, A., Sugawara, S., Kurasawa, N., Saigusa, D., Miura, D., Morikawa-Ichinose, T., and Saito, R. (2016). Metabolic alterations by indoxyl sulfate in skeletal muscle induce uremic sarcopenia in chronic kidney disease. Sci. Rep., 6."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1172\/JCI37672","article-title":"Urea-induced ROS generation causes insulin resistance in mice with chronic renal failure","volume":"120","author":"Du","year":"2010","journal-title":"J. Clin. Investig."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.tem.2011.12.008","article-title":"Linking mitochondrial bioenergetics to insulin resistance via redox biology","volume":"23","author":"Neufer","year":"2012","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1038\/ki.2008.195","article-title":"Fat redistribution and adipocyte transformation in uninephrectomized rats","volume":"74","author":"Zhao","year":"2008","journal-title":"Kidney Int."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1038\/ki.2013.9","article-title":"White adipose tissue overproduces the lipid-mobilizing factor zinc \u03b12-glycoprotein in chronic kidney disease","volume":"83","author":"Pelletier","year":"2013","journal-title":"Kidney Int."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/ki.2009.411","article-title":"Combined effects of ghrelin and higher food intake enhance skeletal muscle mitochondrial oxidative capacity and AKT phosphorylation in rats with chronic kidney disease","volume":"77","author":"Barazzoni","year":"2010","journal-title":"Kidney Int."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Granata, S., Zaza, G., Simone, S., Villani, G., Latorre, D., Pontrelli, P., Carella, M., Schena, F.P., Grandaliano, G., and Pertosa, G. (2009). Mitochondrial dysregulation and oxidative stress in patients with chronic kidney disease. BMC Genom., 10.","DOI":"10.1186\/1471-2164-10-388"},{"key":"ref_108","first-page":"532","article-title":"Skeletal muscle mitochondrial depletion and dysfunction in chronic kidney disease","volume":"6","author":"Yazdi","year":"2013","journal-title":"Int. J. Clin. Exp. Med."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1330","DOI":"10.1038\/ki.2013.473","article-title":"Chronic kidney disease reduces muscle mitochondria and exercise endurance and its exacerbation by dietary protein through inactivation of pyruvate dehydrogenase","volume":"85","author":"Tamaki","year":"2014","journal-title":"Kidney Int."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.semnephrol.2016.05.007","article-title":"Consequences of CKD on functioning","volume":"36","author":"Kittiskulnam","year":"2016","journal-title":"Semin. Nephrol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"102","DOI":"10.3389\/fphys.2015.00102","article-title":"Uremic myopathy: Is oxidative stress implicated in muscle dysfunction in uremia?","volume":"6","author":"Kaltsatou","year":"2015","journal-title":"Front. Physiol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1093\/ndt\/gft070","article-title":"Uraemic sarcopenia: Aetiology and implications","volume":"29","author":"Fahal","year":"2014","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1901","DOI":"10.2215\/CJN.01970309","article-title":"Physical activity and mortality in chronic kidney disease (NHANES III)","volume":"4","author":"Beddhu","year":"2009","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"2074","DOI":"10.1093\/ndt\/gfg325","article-title":"Atrophy of non-locomotor muscle in patients with end-stage renal failure","volume":"18","author":"Sakkas","year":"2003","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"S24","DOI":"10.1053\/j.jrn.2010.05.007","article-title":"Muscle atrophy in chronic kidney disease results from abnormalities in insulin signaling","volume":"20","author":"Price","year":"2010","journal-title":"J. Ren. Nutr."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1046\/j.1525-139X.2002.00083.x","article-title":"Inflammation in end-stage renal disease: Sources, consequences, and therapy","volume":"15","author":"Stenvinkel","year":"2002","journal-title":"Semin. Dial."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1053\/j.ajkd.2015.08.028","article-title":"Metabolic acidosis of CKD: An update","volume":"67","author":"Kraut","year":"2016","journal-title":"Am. J. Kidney Dis."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1053\/j.jrn.2005.07.005","article-title":"Muscle protein metabolism during hemodialysis","volume":"16","author":"Rennie","year":"2006","journal-title":"J. Ren. Nutr."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1146\/annurev.me.26.020175.001333","article-title":"Muscle amino acid metabolism and gluconeogenesis","volume":"26","author":"Ruderman","year":"1975","journal-title":"Annu. Rev. Med."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.arr.2018.07.005","article-title":"The age-related loss of skeletal muscle mass and function: Measurement and physiology of muscle fibre atrophy and muscle fibre loss in humans","volume":"47","author":"Wilkinson","year":"2018","journal-title":"Ageing Res. Rev."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.celrep.2015.12.015","article-title":"The cost of protein production","volume":"14","author":"Kafri","year":"2016","journal-title":"Cell Rep."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"29215","DOI":"10.1074\/jbc.M113.482570","article-title":"The ATP costs and time required to degrade ubiquitinated proteins by the 26 S proteasome","volume":"288","author":"Peth","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_123","first-page":"218","article-title":"Effect of chronic uraemia on skeletal muscle metabolism in man","volume":"8","author":"Thompson","year":"1993","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1038\/ki.1993.124","article-title":"31P NMR spectroscopy investigation of muscle metabolism in hemodialysis patients","volume":"43","author":"Durozard","year":"1993","journal-title":"Kidney Int."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1520","DOI":"10.1093\/ndt\/gfh189","article-title":"Abnormal mitochondrial function and muscle wasting, but normal contractile efficiency, in haemodialysed patients studied non-invasively in vivo","volume":"19","author":"Kemp","year":"2004","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1681\/ASN.V6168","article-title":"Effects of chronic renal failure on enzymes of energy metabolism in individual human muscle fibers","volume":"6","author":"Conjard","year":"1995","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"281","DOI":"10.3109\/00365599709070349","article-title":"Altered muscle energy metabolism in post-absorptive patients with chronic renal failure","volume":"31","author":"Pastoris","year":"1997","journal-title":"Scand. J. Urol. Nephrol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"E219","DOI":"10.1152\/ajpendo.2000.278.2.E219","article-title":"Reduced synthesis of muscle proteins in chronic renal failure","volume":"278","author":"Adey","year":"2000","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1152\/japplphysiol.00556.2011","article-title":"Metabolic and morphometric profile of muscle fibers in chronic hemodialysis patients","volume":"112","author":"Lewis","year":"2012","journal-title":"J. Appl. Physiol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"e12780","DOI":"10.14814\/phy2.12780","article-title":"Mitochondrial dysfunction and oxidative stress in patients with chronic kidney disease","volume":"4","author":"Gamboa","year":"2016","journal-title":"Physiol. Rep."},{"key":"ref_131","first-page":"F1128","article-title":"Chronic kidney disease induces autophagy leading to dysfunction of mitochondria in skeletal muscle","volume":"312","author":"Su","year":"2017","journal-title":"Am. J. Physiol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1681\/ASN.2007091031","article-title":"Mitochondrial DNA injury and mortality in hemodialysis patients","volume":"20","author":"Rao","year":"2009","journal-title":"J. Am. Nephrol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1053\/j.ajkd.2016.05.011","article-title":"CKD and muscle mitochondrial energetics","volume":"68","author":"Roshanravan","year":"2016","journal-title":"Am. J. Kidney Dis."},{"key":"ref_134","first-page":"e6518","article-title":"The impact of immobilisation and inflammation on the regulation of muscle mass and insulin resistance: Different routes to similar end-points","volume":"4","author":"Crossland","year":"2018","journal-title":"J. Physiol."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.tem.2016.04.010","article-title":"CMPF: A biomarker for type 2 diabetes mellitus progression?","volume":"27","author":"Koppe","year":"2016","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"2889","DOI":"10.1016\/j.celrep.2016.02.079","article-title":"Rapid elevation in CMPF may act as a tipping point in diabetes development","volume":"14","author":"Liu","year":"2016","journal-title":"Cell Rep."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"3598","DOI":"10.1172\/JCI86181","article-title":"Urea impairs \u03b2 cell glycolysis and insulin secretion in chronic kidney disease","volume":"126","author":"Koppe","year":"2016","journal-title":"J. Clin. Investig."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1016\/j.cmet.2014.03.008","article-title":"The furan fatty acid metabolite CMPF is elevated in diabetes and induces \u03b2 cell dysfunction","volume":"19","author":"Prentice","year":"2014","journal-title":"Cell Metab."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/11\/2751\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:56:14Z","timestamp":1760187374000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/11\/2751"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,6,5]]},"references-count":138,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2019,6]]}},"alternative-id":["ijms20112751"],"URL":"https:\/\/doi.org\/10.3390\/ijms20112751","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,6,5]]}}}