Studies on the metabolism of insulin by pancreas in vitro. I. Degradation of exogenous insulin by calf pancreas slices.

Abstract

A study was made of the nature and significance of the production by calf pancreas slices of TCA-soluble radioactivity from insulin-I131, as a measure of insulin degradation. Insulin degradation increased with time of incubation, and with tissue and insulin (substrate) concentration. The degrading system showed pH and temperature optima and was heat labile. Inhibition by poisons for —SH-containing enzymes was shown; inhibitors of hepatic "insulinase" also inhibited pancreatic "insulinase". Soybean trypsin inhibitor and cinnamic acid, which prevented the breakdown of insulin by crystalline trypsin, were without effect upon pancreatic "insulinase". Several degradation products were found. The results all support the conclusion that calf pancreas slices contain an active insulin-degrading system which apparently acts by catalyzing proteolytic breakdown of insulin into TCA-soluble fragments. This enzyme system ("insulinase") is similar to, but not identical with, liver "insulinase".