Cardiovascular disease accounts for the majority of the morbidity and mortality patients with diabetes. A complete understanding of the pathways leading to the disturbed metabolism observed in the diabetic heart will provide new insight into the disease and provide novel avenues for therapy. The investigator seeks to determine the role of Glut4 function in the onset of cardiac disease by investigating the effect of a cardiac-specific Glut-4 disruption. This study will provide an important comparison to previous results obtained with the Glut-4 KO mouse in which cardiac function was significantly altered. The specific KO will determine the specific contribution of Glut4 to the heart. The four specific aims to evaluate the cardiac selective deletion of GLUT 4 mouse model are to determine: If whole body glucose tolerance and insulin sensitivity, and cardiac metabolic fuels of lactate, free fatty acids, ketone bodies, and amino acids differ from the wild type. If the expression of other glucose transporters (GLUT 1, 3, and 5) are altered in the hearts of normoglycemic and diabetic mice. The extent of reduction of in vivo cardiac glucose transport in normoglycemic and diabetic mice. The impact on glucose oxidation in vivo in isolated perfused hearts of normoglycemic and diabetic mice.
