Localized calcium influx in pancreatic β-cellsIts significance for Ca2+-dependent insulin secretion from the islets of langerhans

Ca2+ influx through voltage-dependent Ca2+ channels plays a crucial role in stimulus-secretion coupling in pancreatic islet β-cells. Molecular and physiologic studies have identified multiple Ca2+ channel subtypes in rodent islets and insulin-secreting cell lines. The differential targeting of Ca2+ channel subtypes to the vicinity of the insulin secretory apparatus is likely to account for their selective coupling to glucose-dependent insulin secretion. In this article, I review these studies. In addition, I discuss temporal and spatial aspects of Ca2+ signaling in β-cells, the former involving the oscillatory activation of Ca2+ channels during glucose-induced electrical bursting, and the latter involving [Ca2+]i elevation in restricted microscopic “domains”, as well as direct interactions between Ca2+ channels and secretory SNARE proteins. Finally, I review the evidence supporting a possible role for Ca2+ release from the endoplasmic reticulum in glucose-dependent insulin secretion, and evidence to support the existence of novel Ca2+ entry pathways. I also show that the β-cell has an elaborate and complex set of [Ca2+]i signaling mechanisms that are capable of generating diverse and extremely precise [Ca2+]i patterns. These signals, in turn, are exquisitely coupled in space and time to the β-cell secretory machinery to produce the precise minute-to-minute control of insulin secretion necessary for body energy homeostasis.