Localized calcium influx in pancreatic beta-cells: its significance for Ca2+-dependent insulin secretion from the islets of Langerhans

Endocrine. 2000 Dec;13(3):251-62. doi: 10.1385/ENDO:13:3:251.


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, 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 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Calcium / pharmacology
  • Calcium Channels, L-Type / analysis
  • Calcium Channels, L-Type / physiology
  • Calcium Channels, T-Type / analysis
  • Calcium Channels, T-Type / physiology
  • Electric Conductivity
  • Electrophysiology
  • Exocytosis
  • Glucose / pharmacology
  • Humans
  • Insulin / metabolism
  • Insulin Secretion
  • Ion Channel Gating
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / metabolism*


  • Calcium Channels, L-Type
  • Calcium Channels, T-Type
  • Insulin
  • Glucose
  • Calcium