Influence of insulin resistance and amino acid supply on muscle protein turnover in uremia
Mitch, W.E.; May, R.C.; Clark, A.S.; Maroni, B.J.; Kelly, R.A.
Kidney International. Supplement 22: S104-S108
1987
ISSN/ISBN: 0098-6577 PMID: 3480975 Document Number: 302610
Epitrochlearis muscles from male Sprague-Dawley rats weighing 180 to 220 g were incubated to estimate rates of protein synthesis and degradation. Muscles were incubated in Krebs-Henseleit bicarbonate buffer containing 10 mM glucose, 0.5 mM phenylalanine, [U-14C]phenylalanine 0.05 mu Ci/ml and insulin or other factors being studied. To estimate the components of glucose metabolism muscles were incubated with different species of radiolabelled glucose. After 24 h of acute renal failure (ARF) net protein degradation in muscle was increased due to acceleration of protein degradation; protein synthesis was unchanged compared with that in muscles of control rats. After 48 h of ARF protein degradation remained high but protein synthesis was also abnormal. After 48 h of ARF the maximum rates of insulin-stimulated glucose uptake and glycogen synthesis were decreased by 24 and 54%, respectively. In muscles of ARF and control rats the estimated half-maximum rate of glucose uptake and glycogen synthesis occurred at similar insulin concentrations, indicating that ARF depressed the responsiveness of muscle to insulin without substantially affecting insulin sensitivity. The maximum rate of glucose oxidation in muscle was decreased 30% by ARF. ARF also caused a 23% decrease in the total glycogen synthase activity and the fraction of that enzyme in the activated form; those abnormalities persisted during incubation with insulin. ARF did not cause any significant abnormality in glycogen phosphorylase activity in muscle. There was a significant positive correlation between the ratio of glycolysis:glucose uptake and net protein degradation in muscles of fed and starved normal rats and muscles of rats responding to the catabolic stimulus of thermal injury. Other studies examining amino acid availability are also reported.