Glucose metabolism and left ventricular dysfunction are normalized by insulin and islet transplantation in mild...

The aim of the present experimental study in the rat heart was to assess cardiac performance and metabolism in mild diabetes of 2 months' duration (postprandial blood sugar levels of 307 +/- 101 mg/dl and nearly normal fasting blood glucose of 102 +/- 40 mg/dl) using the working rat heart model at physiological workload with a perfusion time of 60 min. We also compared the effect of two forms of therapy for diabetes, islet transplantation and insulin therapy (s.c.), after 2 months. A 36% reduction in glucose utilization is metabolically characteristic for the diabetic heart, mainly caused by a 55% reduced glucose uptake (P < 0.001), but also by a nearly twofold increased lactate and pyruvate production (P < 0.001). This reduced carbohydrate metabolism is accompanied by a 37% reduction of oxygen uptake (P < 0.001) as well as a significant reduction in myocardial ATP and CP levels (P < 0.001), resulting in a significantly reduced cardiac output (P < 0.001). Moreover, the balance of energy reveals that the diabetic heart obtains 46% of its energy requirements for 1 h from endogenous glycogen, whereas the control heart obtains 91% of its energy needs (i.e. preferentially) from exogenous glucose (only 9% from endogenous glycogen). Both investigated therapeutic interventions led to a complete reversibility of the hemodynamic and metabolic alterations, indicating that the cause of diabetic cardiomyopathy in this model of mild and short-term diabetes is due to a defect in cardiac carbohydrate metabolism, which is correctable by insulin administration.