Insulin and Glucagon Degradation by the Same Enzyme

Abstract

An insulin-degrading enzyme has been previously isolated from rat skeletal muscle and highly purified by a series of procedures including affinity chromatography on insulin-agarose. Glucagon-degrading activity was also found in each of the purification steps including the final highly purified material. Insulin- and glucagon-degrading activities were associated with the same band on polyacrylamide gel and both activities were obtained from affinity chromatography on glucagon-agarose. Insulin- and glucagon-degrading activities could not be differentiated by the effect of sulfhydryl reagents, pH, or by heat inactiva-tion. Insulin served as a competitive inhibitor of glucagon degradation (Ki = 1.5 × 10−8M) and glucagon was a competitive inhibitor of insulin degradation (Ki = 5.3 × 10−6M). On the basis of these studies it appears that insulin and glucagon can be degraded by the same enzyme which is found in the soluble fraction of rat skeletal muscle homogenate.