Homologous and heterologous asynchronicity between identified alpha-, beta- and delta-cells within intact islets of Langerhans in the mouse

J Physiol. 1999 May 15;517 ( Pt 1)(Pt 1):85-93. doi: 10.1111/j.1469-7793.1999.0085z.x.

Abstract

1. Using laser scanning confocal microscopy to image [Ca2+]i within intact murine islets of Langerhans, we analysed the [Ca2+]i signals generated by glucose in immunocytochemically identified alpha-, beta- and delta-cells. 2. Glucagon-containing alpha-cells exhibited [Ca2+]i oscillations in the absence of glucose, which petered out when islets were exposed to high glucose concentrations. 3. Somatostatin-containing delta-cells were silent in the absence of glucose but concentrations of glucose as low as 3 mM elicited oscillations. 4. In pancreatic beta-cells, a characteristic oscillatory calcium pattern was evoked when glucose levels were raised from 3 to 11 mM and this was synchronized throughout the beta-cell population. Remarkably, [Ca2+]i oscillations in non-beta-cells were completely asynchronous, both with respect to each other and to beta-cells. 5. These results demonstrate that the islet of Langerhans behaves as a functional syncytium only in terms of beta-cells, implying a pulsatile secretion of insulin. However, the lack of a co-ordinated calcium signal in alpha- and delta-cells implies that each cell acts as an independent functional unit and the concerted activity of these units results in a smoothly graded secretion of glucagon and somatostatin. Understanding the calcium signals underlying glucagon and somatostatin secretion may be of importance in the treatment of non-insulin-dependent diabetes mellitus since both glucagon and somatostatin appear to regulate insulin release in a paracrine fashion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium Signaling / drug effects
  • Calcium Signaling / physiology*
  • Glucagon / metabolism
  • Glucose / pharmacology
  • Immunohistochemistry
  • In Vitro Techniques
  • Insulin / metabolism*
  • Insulin Secretion
  • Islets of Langerhans / cytology*
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / physiology*
  • Mice
  • Microscopy, Confocal
  • Oscillometry
  • Somatostatin / metabolism

Substances

  • Insulin
  • Somatostatin
  • Glucagon
  • Glucose