, Volume 32, Issue 4, pp 235-243

Glucose metabolism and left ventricular dysfunction are normalized by insulin and islet transplantation in mild diabetes in the rat

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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.