Regulation of Intracellular Ca²⁺ Stores by Multiple Ca²⁺-Releasing Messengers

Abstract

Although glucose-elicited insulin secretion depends on Ca²⁺ entry through voltage-gated Ca²⁺ channels in the surface cell membrane of the pancreatic β-cell, there is also ample evidence for an important role of intracellular Ca²⁺ stores, particularly in relation to hormone- or neurotransmitter-induced insulin secretion. There is now direct evidence for Ca²⁺ entry-induced release of Ca²⁺ from the endoplasmic reticulum in neurons, but with regard to glucose stimulation of β-cells, there is conflicting evidence about the operation of such a process. This finding suggests that the sensitivity of the Ca²⁺ 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 Ca²⁺ release. Here we focus on the possible combinatorial roles of inositol 1,4,5-trisphosphate, cyclic ADP-ribose, and nicotinic acid adenine dinucleotide phosphate in β-cell function.