Multisite control of insulin release by glucose

Henquin, Jean-Claude [UCL] Gembal, M. [UCL] de Timary, Philippe [UCL] Gao, Z Y [UCL] Warnotte, Catherine [UCL] Gilon, Patrick [UCL]

Glucose controls insulin release by beta-cells at two sites at least. By controlling the membrane potential, it controls the influx of Ca2+ and the rise in cytoplasmic Ca2+ which triggers exocytosis. At this level, the principal targets of glucose are the K(+)-ATP channels whose activity may be modulated by changes in the ATP/ADP ratio. A second, newly identified, mechanism of regulation is independent of changes in beta-cell membrane potential and of changes in Cai2+. It is not sufficient to induce insulin release, but serves to increase the response. This appears to be achieved through an amplification of the effectiveness of Cai2+ on the secretory process and may also depend on the changes in energy state of beta-cells.