title: Postreceptor myocardial metabolic defect in a rat model of non-insulin-dependent diabetes mellitus.
abstract: Hearts isolated from non-insulin-dependent diabetic rats were found to exhibit reduced rates of basal and insulin-stimulated glucose metabolism. Since tissue levels of fructose 1,6-bisphosphate are significantly reduced in the diabetic heart, it was concluded that phosphofructokinase may be inhibited. However, neither glycogen nor glucose 6-phosphate accumulated in the myocyte, indicating that the phosphofructokinase reaction was not a bottleneck diverting substrate away from glycolysis. The other major factor contributing to decreased glycolytic flux in the diabetic heart is the impairment in glucose transport. Both basal and insulin-stimulated transport of 3-O-methyl-D-glucose was 30% less in the diabetic heart. While insulin sensitivity was unaltered in the diabetic rat, insulin responsiveness was decreased, indicating that the impairment in insulin-stimulated hexose transport was caused by a post-receptor defect. The net result of these abnormalities in glucose metabolism is a significant reduction in the rate of ATP synthesis by the diabetic heart.
mesh_terms: D019325:3-O-Methylglucose; D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D004195:Disease Models, Animal; D005635:Fructosediphosphates / Q000032:analysis; D005947:Glucose / Q000032:analysis / Q000378:metabolism; D019298:Glucose-6-Phosphate; D005958:Glucosephosphates / Q000032:analysis; D006321:Heart / Q000187:drug effects; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D008297:Male; D008757:Methylglucosides / Q000378:metabolism; D009206:Myocardium / Q000032:analysis / Q000378:metabolism*; D010732:Phosphofructokinase-1 / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D005635:Fructosediphosphates; D005958:Glucosephosphates; D007328:Insulin; D008757:Methylglucosides; D019325:3-O-Methylglucose; D019298:Glucose-6-Phosphate; D010732:Phosphofructokinase-1; D005947:Glucose