Localized calcium influx in pancreatic β-cells -: Its 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 beta -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 beta -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, 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 beta -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 beta -cell secretory machinery to produce the precise minute-to-minute control of insulin secretion necessary for body energy homeostasis.