Dual effect of cell-cell contact disruption on cytosolic calcium and insulin secretion

Endocrinology. 2008 May;149(5):2494-505. doi: 10.1210/en.2007-0974. Epub 2008 Jan 24.

Abstract

Cell-to-cell interactions play an important role in insulin secretion. Compared with intact islets, dispersed pancreatic beta-cells show increased basal and decreased glucose-stimulated insulin secretion. In this study, we used mouse MIN6B1 cells to investigate the mechanisms that control insulin secretion when cells are in contact with each other or not. RNAi-mediated silencing of the adhesion molecule E-cadherin in confluent cells reduced glucose-stimulated secretion to the levels observed in isolated cells but had no impact on basal secretion. Dispersed cells presented high cytosolic Ca(2+) activity, depolymerized cytoskeleton and ERK1/2 activation in low glucose conditions. Both the increased basal secretion and the spontaneous Ca(2+) activity were corrected by transient removal of Ca(2+) or prolonged incubation of cells in low glucose, a procedure that restored the ability of dispersed cells to respond to glucose (11-fold stimulation). In conclusion, we show that dispersed pancreatic beta-cells can respond robustly to glucose once their elevated basal secretion has been corrected. The increased basal insulin secretion of dispersed cells is due to spontaneous Ca(2+) transients that activate downstream Ca(2+) effectors, whereas engagement of cell adhesion molecules including E-cadherin contributes to the greater secretory response to glucose seen in cells with normal intercellular contacts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cadherins / antagonists & inhibitors
  • Cadherins / metabolism
  • Calcium / metabolism*
  • Calcium Channels / metabolism
  • Calcium Channels / physiology
  • Cell Adhesion / drug effects
  • Cell Adhesion / genetics
  • Cell Communication / physiology*
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Contact Inhibition / physiology*
  • Cytosol / metabolism*
  • Down-Regulation / drug effects
  • Glucose / pharmacology
  • Insulin / metabolism*
  • Insulin Secretion
  • Insulin-Secreting Cells / drug effects
  • Insulin-Secreting Cells / metabolism
  • Insulin-Secreting Cells / physiology
  • Mice
  • Oligonucleotide Array Sequence Analysis
  • Proinsulin / metabolism
  • Protein Transport
  • RNA, Small Interfering / pharmacology

Substances

  • Cadherins
  • Calcium Channels
  • Insulin
  • RNA, Small Interfering
  • Proinsulin
  • Glucose
  • Calcium