Myocardial insulin resistance, metabolic stress and autophagy in diabetes

Abstract

Clinical studies in humans strongly support a link between insulin resistance and non-ischaemic heart failure. The occurrence of a specific insulin-resistant cardiomyopathy, independent of vascular abnormalities, is now recognized. The progression of cardiac pathology linked with insulin resistance is poorly understood. Cardiac insulin resistance is characterized by reduced availability of sarcolemmal Glut-4 transporters and consequent lower glucose uptake. A shift away from glycolysis towards fatty acid oxidation for ATP supply is apparent and is associated with myocardial oxidative stress. Reliance of cardiomyocyte excitation-contraction coupling on glycolytically derived ATP supply potent..