title: Glucose metabolism and left ventricular dysfunction are normalized by insulin and islet transplantation in mild diabetes in the rat.
abstract: 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.
authors: Medical Clinic III and Polyclinic, University of Giessen, Rodthohl, Giessen, Germany.
authors: D
authors: D
authors: Stroedter
authors: T
authors: T
authors: Schmidt
authors: R G
authors: RG
authors: Bretzel
authors: K
authors: K
authors: Federlin
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D002302:Cardiac Output; D009202:Cardiomyopathies / Q000378:metabolism / Q000503:physiopathology; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000503:physiopathology* / Q000601:surgery; D004734:Energy Metabolism; D005947:Glucose / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D066298:In Vitro Techniques; D007328:Insulin / Q000627:therapeutic use*; D016381:Islets of Langerhans Transplantation / Q000502:physiology*; D007773:Lactates / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption; D010725:Phosphocreatine / Q000378:metabolism; D011773:Pyruvates / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D014280:Triglycerides / Q000378:metabolism; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology*
chemical_list: D007328:Insulin; D007773:Lactates; D011773:Pyruvates; D014280:Triglycerides; D010725:Phosphocreatine; D000255:Adenosine Triphosphate; D006003:Glycogen; D005947:Glucose