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

• Published in: Endocrine Vol. 13; no. 3; pp. 251 - 262
• Main Author: Satin, L S
• Format: Journal Article
• Language: English
• Published: United States 01.12.2000
• Subjects: 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
• ISSN: 1355-008X; 1559-0100
• 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.