Insulin secretion plays a pivotal role in glucose homeostasis. An increased rate of insulin release is the only efficient means by which the organism can rapidly decrease circulating glucose concentration. By contrast, several neurohormonal factors can promote elevations in blood glucose. Alterations of pancreatic P-cell function result in metabolic disorders that are most often manifested in diabetes mellitus or in hypoglycemic syndromes. D-Glucose is the preeminent regulator of insulin secretion and biosynthesis; it is the only nutrient stimulus that activates the secretory process in vitro at concentrations within the physiological range. However, many additional factors regulate insulin secretion. Thus various fuel molecules (ie, other carbohydrates, some amino acids, ketone bodies, and fatty acids) and neurohormonal signals regulate secretory function.

Significant advances have been made over the past few years in our understanding of some aspects of signal-transducing mechanisms in the, &cell. We begin to comprehend how fuel and neurotransmitter stimuli induce variations in intracellular factors to which second messenger functions have been ascribed and how the signaling network in the, &cell is regulated. Over the past four years, this progress has largely been made possible by the application to P-cell research of several novel techniques and concepts. These include patch clamping, which allows direct determination of ion channel activities; Ca’+-sensitive dyes and Ca2+ electrodes, which permit direct determination of free Ca2+; and various techniques of cell permeabilization, which allow direct access of small molecules to the cytosol. In addition, the availability of clonal lines of insulin-secreting cells that retain sensitivity to some secretagogues facilitated biochemical and biophysical studies of, &cells. Because clonal P-cells are readily available, two major limitations in islet studies have been partly overcome, ie, the small amount of material that can be obtained from pancreatic islets and the cellular heterogeneity of islet tissue. The recent success in obtaining pure, &cells by fluorescent cell sorting will undoubtedly contribute to progress in this area. The discovery of phospholipid-derived second messengers greatly expanded the conceptual foundation of cell stimulus-response coupling research.