Factors concerned with insulin synthesis and release

Abstract

The daily insulin production of the [beta]-cells of the islets of Langerhans is approximately 50 units of insulin. The normal stimulus for this production of insulin is the concentration of glucose perfusing the islets. The role of other hexoses and further metabolism of glucose in the stimulation of insulin release by the pancreas is considered. Other substances such as the sulfonylureas and the amino acid leucine have also been demonstrated to have effects on insulin release by the [beta]-cells. The histologic and electron microscopic picture associated with insulin release and synthesis in the [beta]-cells is reviewed. Although concentration of glucose perfusing the islets is thought to be the primary stimulus for insulin release, the biochemical steps involved in such control are not known. Glucose uptake by slices of islet cell tumors was not inordinately large. Evidence is reviewed which indicates the presence of both the Embden-Meyerhof and the hexose monophosphate pathway for glucose metabolism in islet tissue. Histochemical methods as well as direct enzyme assays have also revealed the presence of some of the enzymes involved in both of these metabolic pathways. In vitro metabolic and enzyme assays also indicate the presence of the tricarboxylic acid cycle in islet tissue. Several enzymes involved in amino acid metabolism have also been measured in islet cell tissue. Studies using the islet cell organ of certain fish have demonstrated the incorporation of radioactivity from glucose into amino acids and into a protein which has many of the characteristics of insulin. Increasing the glucose concentration in the incubation medium of fish islets was associated with an increase in glucose oxidation and the glucose incorporation into acid ethanol extracible protein. The effects of various factors which are thought to influence insulin secretion and release on the various metabolic parameters of islet cell tissue are reviewed. Although some of the metabolic processes of [beta]-cells have been studied, current knowledge does not permit one to delineate the steps whereby insulin synthesis or release is influenced by various factors.