Ca2+ microdomains and the control of insulin secretion

Cell Calcium. Nov-Dec 2006;40(5-6):539-51. doi: 10.1016/j.ceca.2006.08.015. Epub 2006 Oct 9.


Nutrient-induced increases in intracellular free Ca(2+) concentrations are the key trigger for insulin release from pancreatic islet beta-cells. These Ca(2+) changes are tightly regulated temporally, occurring as Ca(2+) influx-dependent baseline oscillations. We explore here the concept that locally high [Ca(2+)] concentrations (i.e. Ca(2+) microdomains) may control exocytosis via the recruitment of key effector proteins to sites of exocytosis. Importantly, recent advances in the development of organelle- and membrane-targeted green fluorescent protein (GFP-) or aequorin-based Ca(2+) indicators, as well as in rapid imaging techniques, are providing new insights into the potential role of these Ca(2+) microdomains in beta-cells. We summarise here some of the evidence indicating that Ca(2+) microdomains beneath the plasma membrane and at the surface of large dense core vesicles may be important in the normal regulation of insulin secretion, and may conceivably contribute to "ATP-sensitive K(+)-channel independent" effects of glucose. We also discuss evidence that, in contrast to certain non-excitable cells, direct transfer of Ca(2+) from the ER to mitochondria via localised physical contacts between these organelles is relatively less important for efficient mitochondrial Ca(2+) uptake in beta-cells. Finally, we discuss evidence from single cell imaging that increases in cytosolic Ca(2+) are not required for the upstroke of oscillations in mitochondrial redox state, but may underlie the reoxidation process.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Calcium / physiology*
  • Cell Membrane / physiology
  • Cell Membrane / ultrastructure
  • Endoplasmic Reticulum / metabolism
  • Exocytosis / physiology
  • Glucose / pharmacology
  • Insulin / metabolism*
  • Insulin Secretion
  • Insulin-Secreting Cells / physiology*
  • Membrane Microdomains / physiology*
  • Mice
  • Mitochondria / metabolism
  • Munc18 Proteins / physiology
  • Protein Kinase C / physiology
  • Secretory Vesicles / physiology
  • Secretory Vesicles / ultrastructure


  • Insulin
  • Munc18 Proteins
  • Protein Kinase C
  • Glucose
  • Calcium