{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:08:27Z","timestamp":1785416907772,"version":"3.56.0"},"reference-count":79,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2020,3,31]],"date-time":"2020-03-31T00:00:00Z","timestamp":1585612800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Although the presence of cardiac dysfunction and cardiomyopathy in chronic diabetes has been recognized, the pathophysiology of diabetes-induced metabolic and subcellular changes as well as the therapeutic approaches for the prevention of diabetic cardiomyopathy are not fully understood. Cardiac dysfunction in chronic diabetes has been shown to be associated with Ca2+-handling abnormalities, increase in the availability of intracellular free Ca2+ and impaired sensitivity of myofibrils to Ca2+. Metabolic derangements, including depressed high-energy phosphate stores due to insulin deficiency or insulin resistance, as well as hormone imbalance and ultrastructural alterations, are also known to occur in the diabetic heart. It is pointed out that the activation of the sympathetic nervous system and renin\u2013angiotensin system generates oxidative stress, which produces defects in subcellular organelles including sarcolemma, sarcoplasmic reticulum and myofibrils. Such subcellular remodeling plays a critical role in the pathogenesis of diabetic cardiomyopathy. In fact, blockade of the effects of neurohormonal systems has been observed to attenuate oxidative stress and occurrence of subcellular remodeling as well as metabolic abnormalities in the diabetic heart. This review is intended to describe some of the subcellular and metabolic changes that result in cardiac dysfunction in chronic diabetes. In addition, the therapeutic values of some pharmacological, metabolic and antioxidant interventions will be discussed. It is proposed that a combination therapy employing some metabolic agents or antioxidants with insulin may constitute an efficacious approach for the prevention of diabetic cardiomyopathy.<\/jats:p>","DOI":"10.3390\/ijms21072413","type":"journal-article","created":{"date-parts":[[2020,4,1]],"date-time":"2020-04-01T03:44:13Z","timestamp":1585712653000},"page":"2413","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":73,"title":["Role of Oxidative Stress in Metabolic and Subcellular Abnormalities in Diabetic Cardiomyopathy"],"prefix":"10.3390","volume":"21","author":[{"given":"Naranjan S.","family":"Dhalla","sequence":"first","affiliation":[{"name":"Institute of Cardiovascular Sciences, St. Boniface Hospital Albrechtsen Research Centre, Winnipeg, MB R2H 2A6, Canada"},{"name":"Department of Physiology and Pathophysiology, College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0J9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1765-0942","authenticated-orcid":false,"given":"Anureet K.","family":"Shah","sequence":"additional","affiliation":[{"name":"Department of Kinesiology, Nutrition and Food Science, California State University, Los Angeles, CA 90032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8307-2760","authenticated-orcid":false,"given":"Paramjit S.","family":"Tappia","sequence":"additional","affiliation":[{"name":"Asper Clinical Research Institute, St. Boniface Hospital, Winnipeg, MB R2H 2A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,3,31]]},"reference":[{"key":"ref_1","first-page":"776","article-title":"Diabetic cardiomyopathy: Experimental and clinical observations","volume":"91","author":"Regan","year":"1994","journal-title":"N. 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