STIMULUS-SECRETION COUPLING IN PANCREATIC BETA-CELLS

insulin secretion is triggered by a rise in the intracellular Ca2+ con centration that results from the activation of voltage-gated Ca2+ chan nels in the p-cell plasma membrane. Multiple types of beta-cell Ca2+ c hannel have been identified in both electrophysiological and molecular biological studies, but it appears that the L-type Ca2+ channel plays a dominant role in regulating Ca2+ influx. Activity of this channel i s potentiated by protein kinases A and C and is inhibited by GTP-bindi ng proteins, which may mediate the effects of potentiators and inhibit ors of insulin secretion on Ca2+ influx, respectively. The mechanism b y which elevation of intracellular Ca2+ leads to the release of insuli n granules is not fully understood but appears to involve activation o f Ca2+/calmodulin-dependent protein kinase. Phosphorylation by either protein kinase A or C, probably at different substrates, potentiates i nsulin secretion by acting at some late stage in the secretory process . There is also evidence that small GTP-binding proteins are involved in regulating exocytosis in beta cells. The identification and charact erisation of the proteins involved in exocytosis in beta cells and cla rification of the mechanism(s) of action of Ca2+ is clearly an importa nt goal for the future. (C) 1994 Wiley-Liss, Inc.