MULTISITE CONTROL OF INSULIN RELEASE BY GLUCOSE

Glucose controls insulin release by beta-cells at two sites at least. By controlling the membrane potential, it controls the influx of Ca2and the rise in cytoplasmic Ca-1(2+) which triggers exocytosis. At thi s level, the principal targets of glucose are the K+-ATP channels whos e activity may be modulated lay changes in the ATP/ADP ratio. A second . newly identified, mechanism or regulation is independent of changes in beta-cell membrane potential and of changes in Ca-1(2+). It is not sufficient to induce insulin release. but serves to increase the respo nse. This appears to be achieved through an amplification of the effec tiveness of Ca-1(2+) an the secretory process and may also depend on t he changes in energy state of beta-cells.