Section 3 :-Cell Stimulus-Secretion Coupling : K ATP Channels and Ca 2 Regulation of Intracellular Ca 2 Stores by Multiple Ca 2-Releasing Messengers

Although glucose-elicited insulin secretion depends on Ca entry through voltage-gated Ca channels in the surface cell membrane of the pancreatic -cell, there is also ample evidence for an important role of intracellular Ca stores, particularly in relation to hormoneor neurotransmitter-induced insulin secretion. There is now direct evidence for Ca entry–induced release of Ca from the endoplasmic reticulum in neurons, but with regard to glucose stimulation of -cells, there is conflicting evidence about the operation of such a process. This finding suggests that the sensitivity of the Ca release channels in the endoplasmic reticulum membrane varies under different conditions and therefore is regulated. Recent evidence from studies of pancreatic acinar cells has revealed combinatorial roles of multiple messengers in setting the sensitivity of the endoplasmic reticulum for Ca release. Here we focus on the possible combinatorial roles of inositol 1,4,5trisphosphate, cyclic ADP-ribose, and nicotinic acid adenine dinucleotide phosphate in -cell function. Diabetes 51 (Suppl. 3):S349–S357, 2002