SUBCELLULAR REMODELING AND HEART DYSFUNCTION IN CHRONIC DIABETES

Heart dysfunction in chronic diabetes has been observed to be associat ed with depressed myofibrillar adenosine triphosphatase activities as well as abnormalities in the sarcoplasmic reticular and sarcolemmal ca lcium transport processes. The evidence has been presented to show tha t alterations in the expression of myosin isozymes and regulatory prot eins as well as myosin phosphorylation contribute to the development o f myofibrillar remodeling in the diabetic heart. Defects in sarcoplasm ic reticular and sarcolemmal calcium transport appear to be due to the accumulation of lipid metabolites in the membrane. Different agents, such as calcium-antagonists, beta-adrenoceptor blockers, angiotensin c onverting enzyme inhibitors, metabolic interventions and antioxidants, have been reported to exert beneficial effects in preventing subcellu lar remodeling and cardiac dysfunction in chronic diabetes. Clinical a nd experimental investigations have suggested that increased sympathet ic activity, activated cardiac renin-angiotensin system, myocardial is chemia/functional hypoxia and elevated levels of glucose for a prolong ed period, due to insulin deficiency, result in oxidative stress. It i s proposed that oxidative stress associated with a deficit in the stat us of the antioxidant defense system may play a critical role in subce llular remodeling, calcium-handling abnormalities and subsequent diabe tic cardiomyopathy. (C) 1998 Elsevier Science B.V. All rights reserved .