Intermediary Metabolism and Insulin Secretion from Isolated Rat Islets of Langerhans

Abstract

How the pancreatic beta cells recognize glucose as an islet stimulant and respond appropriately by altering their rate of insulin secretion are unknown. Attention over the last 15 yr has focused primarily on the metabolic degradation of the hexose, and such studies have led to the formulation of the substrate-site or metabolic theory of stimulated insulin secretion. Simply stated, this theory evisions a metabolite of glucose or a cofactor generated during glucose catabolism, and not the intact glucose molecule itself, as being the trigger for insulin secretion. A direct effect of glucose on a membrane or on a cytosolic receptor (glucoreceptor theory) may account for secretion. Combinations of these 2 theories have also been considered. The experimental evidence supporting the substrate-site theory is considerable. While most experimental evidence appeared to strengthen the metabolic theory substantially, some observations were not easily reconciled with it. Rapid advances have been made over the last few years in understanding of the physiology of the .beta.-cells. The present review focuses primarily on recent studies and their attempts to establish the sequence of events that intervene between glucose and the secretion of insulin from the islets. Particular attention is given to the metabolism of glucose and other islet stimulants.