The heart in type 1 diabetes: Characterization of structure, function and exercise-induced benefits in diabetic cardiomyopathy

Abstract

Diabetes mellitus compromises the structure and function of the cardiovascular system. We have characterized the structural and functional abnormalities of the diabetic myocardium using streptozotocin-induced (generic) and autoimmune-intolerant (specific) rat models of type 1 diabetes. In addition, we have identified potential structural, functional, and molecular correlates of exercise-induced benefits in the diabetic myocardium. The experimental models demonstrated highly compromised structure and function of myocardium in the diabetic state. Using structural magnetic resonance imaging, we were able to demonstrate the abnormal heart wall dynamics resulting from myocardial stiffness; a characteristic of the fibrotic heart in diabetes. Furthermore, the diabetic left ventricle manifested cardiac cycle abnormalities detectable via functional magnetic resonance imaging. Systolic and diastolic left ventricular functions were compromised in the diabetic heart. Microscopically, increased accumulation of interstitial collagen and decreased distribution of mitochondria were identifiable as the cardinal features of the diabetic myocardium. Endurance training, however, attenuated the structural and functional defects of the diabetic heart. Training prevented the development of myocardial fibrosis and loss of viable mitochondria in the diabetic heart. Training also ameliorated the systolic and diastolic dysfunctions of the ventricular pump in diabetes. Moreover, training-induced benefits were evident at the molecular level as decreased expression of myocardial protein kinase c (β II isoform); a critical protein implicated in the pathogenesis of diabetic cardiomyopathy. In summary, these investigations demonstrate the vulnerability of the heart for failure and the efficacy of exercise in attenuating the major cardiac abnormalities in type 1 diabetes.