Modulation of 125I-insulin degradation by receptors in liver plasma membranes

Abstract

This study investigated the interactions of insulin with receptors in a purified mouse liver plasma membrane. Two processes were found when insulin was incubated with the liver plasma membranes at 30°C; 1) the binding of insulin to these membranes and 2) the degradation of insulin by one or more associated insulinases or proteases. These two activities were physically separated, analyzed, and it was found that bound insulin is a substrate for insulin degradation. In addition, the rate of degradation of free insulin in solution was found to be 1.1% degraded insulin/available insulin/min in a 30 minute period. This rate is compared to 25.3% degraded insulin/available insulin/min under similar conditions when insulin is bound to the plasma membranes. Thus, insulin binding was shown to aid in its degradation. These results suggest that a specific binding by at least one of the receptors for insulin orients the molecule such that its degradation is facilitated.