Inhibition by Insulin of Valine Turnover in Liver

Abstract

Abstract Proteolysis was assessed during perfusion of isolated livers of nonfasted rats from the turnover of free valine, measured after single pulse additions of l-valine-1-14C to the perfusate, and from the release of label from livers previously labeled with l-valine-1-14C in vivo and then perfused with 15 mm unlabeled valine to minimize reincorporation. Since valine is not synthesized in the rat and was shown not to be metabolized significantly in these experiments, it could be assumed that any net gain or loss of free valine would reflect net changes in the protein content of the system. In control experiments, free valine accumulated slowly for 15 to 30 min; the rate then spontaneously increased rather abruptly and remained elevated. Since the utilization of extracellular valine by protein synthesis did not fall off with time, the spontaneous increase in valine accumulation was ascribed to an enhancement of proteolysis. Insulin in vitro completely inhibited this spontaneous net increase and also inhibited the release of label from previously labeled livers. No specific hormonal effects were noted on the incorporation of free valine into protein or its distribution in intra- and extracellular water. The inhibitory effect of insulin, which was sustained for periods up to 180 min of perfusion, was estimated to represent 1.0% of total liver protein per hour.