Inhibition of Glucose-Stimulated Insulin Release in the Perfused Rat Pancreas by Parathyroid Secretory Protein-I (Chromogranin-A)*

Abstract

The effect of graded doses (10-10-10-8 M) of highly purified bovine parathyroid secretory protein-I (SP-I; chromogranin-S) or synthetic porcine pancreastatin on glucose-stimulated insulin release in the perfused rat pancreas was examined. SP-I (10-9 M) inhibited the first phase of glucose-stimulated insulin release, and 10-8 M SP-I inhibited both the first and second phases of glucose-stimulated insulin release; 10-10 M SP-I was inactive. In comparison, pancreastatin at 10-10 M inhibited the first phase of insulin release, and at 10-9 and 10-8 M, pancreastatin inhibited both phases of insulin release. The inhibition by SP-I was achieved at concentrations that normally exist in the general circulation of man. These and other data suggest that circulating SP-I plays a physiological role in the regulation of insulin secretion.