Insulin Secretion Studied in the Perfused Rat Pancreas: I. Effect of Tolbutamide, Leucine and Arginine; Their Interaction with Diazoxide, and Relation to Glucose

Abstract

Glucose produced a diphasic pattern of insulin secretion in the perfused rat pancreas. Both phases were blocked by diazoxide. Tolbutamide alone produced a monophasic insulin secretion which was decreased by diazoxide on an equimolar basis. When tolbutamide was added to a perfusion containing glucose and diazoxide, it reversed the blocking effect of diazoxide on glucose by reestablishing the diphasic pattern of glucose-stimulated insulin secretion. This effect was also produced in an equimolar fashion. Leucine induced a diphasic pattern of insulin secretion. When perfused together with glucose, an additive effect was apparent in both phases. Diazoxide blocked the secretion of insulin stimulated by leucine alone or by leucine plus glucose. Arginine (16 mM) failed to stimulate insulin secretion, but a clear increase was observed at 26 mM concentration. An additive effect of arginine and glucose was observed in the presence or absence of 10 mg. per cent diazoxide, but was blocked by increased diazoxide concentration (25 mg. per cent). The results show that the diazoxide effect on the arginine-induced insulin secretion is related to the concentration of diazoxide used, and suggests that the stimulatory action of arginine and glucose is channelled through one identical mechanism, triggering insulin release in the beta cell.