Specific defects in insulin-mediated muscle metabolism in acute uremia.
The mechanisms underlying the abnormal insulin-mediated muscle glucose metabolism occurring in acute uremia (ARF) have not been identified. To characterize the defects, insulin dose-response curves for glucose uptake, glycogen synthesis, glucose oxidation, glycolysis, and lactate release were measured in incubated rat epitrochlearis muscles. ARF did not affect insulin sensitivity, but decreased the responsiveness to insulin of glucose uptake, glycogen synthesis, and glucose oxidation. Glycogen synthesis was subnormal at all levels of insulin and at the maximal insulin concentration; it was 54% lower in muscles of ARF compared to control rats. This inhibition of glycogen synthesis in ARF could be caused by a 23% decrease in the total activity of muscle glycogen synthase and the percentage of enzyme in the activated form. Glycogen phosphorylase activity was unchanged by ARF. ARF also increased the ratio of muscle lactate release to glucose uptake at concentrations of insulin from 10 to 10(4) microU/ml. In the absence and presence of insulin, muscle protein degradation was increased by ARF. In individual muscles incubated with insulin, the rate of proteolysis was correlated with the ratio of lactate release to glucose uptake (r = + 0.82; P less than 0.01). From the insulin dose-response relationships and changes in enzyme activities, we conclude that ARF increases protein degradation in muscle and causes abnormal insulin-mediated glucose metabolism. The abnormalities in glucose metabolism are caused by changes in post-receptor events.
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D006003:Glycogen / Q000096:biosynthesis; D007328:Insulin / Q000494:pharmacology*; D007333:Insulin Resistance; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008297:Male; D009132:Muscles / Q000187:drug effects / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014511:Uremia / Q000378:metabolism*
D007328:Insulin; D007773:Lactates; D011506:Proteins; D019344:Lactic Acid; D006003:Glycogen; D005947:Glucose