Dissociation of glucose stimulation of somatostatin and insulin release from glucose inhibition of glucagon release in the isolated perfused rat pancreas.

Abstract

This study investigated the modulating role of glucose on 5 mM arginine stimulation of insulin, somatostatin, and glucagon release from the isolated perfused rat pancreas. As the concentration of glucose was increased linearly from 50 to 300 mg/dl, arginine-stimulated glucagon release was inhibited, with half-maximal inhibition occurring at 84 mg/dl glucose. As glucose increased above 80 mg/dl, somatostatin and insulin release was initiated and they continued to increase in a nearly parallel fashion during the glucose gradient (300 mg/dl). When 5 mM arginine was presented "en block" against varying backgrounds of glucose (30, 60, 75, 90, 120, 150, and 300 mg/dl), glucagon release was diminished in the presence of glucose concentrations greater than 60 mg/dl. Arginine elicited insulin release at all glucose concentrations and was significantly augmented in the presence of glucose greater than 90 mg/dl. Arginine-stimulated somatostatin release was detectable in the 90-mg/dl glucose group and was significantly augmented in the 120- and 150-mg/dl glucose treatment groups. In conclusion, these studies indicate that glucose modulates the arginine effect on alpha, beta, and delta cells; and alpha cells have a lower threshold to glucose than beta and delta cells. Glucose inhibits arginine-stimulated glucagon release in the absence of a detectable glucose or arginine stimulation of somatostatin release. Thus, glucose appears to play a major role in the control of the putative hormonal influence among the islet cells.