Enhanced Myocardial Glucose Delivery Accelerates Development of Mitochondrial Dysfunction in the Diabetic Heart

Cardiac glucose delivery and utilization are reduced in diabetes despite hyperglycemia. Mitochondrial dysfunction contributes to heart failure in diabetic patients. The loss of mitochondrial substrate flexibility in regulating cellular and cardiac function is actively under investigation. To determine the direct role of glucose delivery in the maintenance of cardiac contractile and mitochondrial function we generated transgenic mice with inducible cardiomyocyte-specific expression of the glucose transporter 4 (mG4H). We examined mice that were made hyperglycemic with low dose streptozotocin (STZ)-induced diabetes 2 weeks prior to increasing intracellular glucose uptake for and additional 2 weeks by transgene induction.