Skeletal Muscle Protein and Amino Acid Metabolism in Experimental Chronic Uremia in the Rat: ACCELERATED ALANINE AND GLUTAMINE FORMATION AND RELEASE

The kinetics and factors regulating alanine and glutamine formation and release were investigated in skeletal muscle preparations from control and experimentally uremic rats. These preparations maintained phosphocreatine and ATP levels in vitro which closely approximated levels found in vivo. Alanine and glutamine release from uremic muscle were increased 45.8 and 36.0%, respectively, but tissue levels were unaltered. The increased release of alanine by uremic muscle was not accounted for by decreased rates of medium alanine reutilization via oxidation to CO₂ or incorporation into muscle protein. The maximal capacity of added amino acids such as aspartate, cysteine, leucine, and valine to stimulate net alanine and glutamine formation was the same in uremic and control muscle. Epitrochlearis preparations were partially labeled in vivo with [guanido-¹⁴C]-arginine. On incubation, preparations from uremic animals showed a 54.6% increase in the rate of loss of ¹⁴C-label in acid precipitable protein. Correspondingly, these same uremic preparations showed a 62.7% increase in ¹⁴C-label appearance in the acid-soluble fraction of muscle and in the incubation media. Insulin decreased alanine and glutamine release to an extent threefold greater in uremic than in control preparations, and increased muscle glucose uptake approximately threefold in all preparations. Although basal rates of [4,5-³H]leucine incorporation into protein were decreased 25% in uremic muscles as compared with control muscles, insulin stimulated [³H]leucine incorporation nearly equally in both preparations.