Dual effect of cell-cell contact disruption on cytosolic calcium and insulin secretion.
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.
Jaques
Fabienne
F
Department of Genetic Medicine and Development, University of Geneva Medical Center, 1211 Geneva-4, Switzerland. fabienne.jaques@medecine.unige.ch
Jousset
Hélène
H
Tomas
Alejandra
A
Prost
Anne-Lise
AL
Wollheim
Claes B
CB
Irminger
Jean-Claude
JC
Demaurex
Nicolas
N
Halban
Philippe A
PA
D000818:Animals; D015820:Cadherins / Q000037:antagonists & inhibitors / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism / Q000502:physiology; D002448:Cell Adhesion / Q000187:drug effects / Q000235:genetics; D002450:Cell Communication / Q000502:physiology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003260:Contact Inhibition / Q000502:physiology*; D003600:Cytosol / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D011384:Proinsulin / Q000378:metabolism; D021381:Protein Transport; D034741:RNA, Small Interfering / Q000494:pharmacology
D015820:Cadherins; D015220:Calcium Channels; D007328:Insulin; D034741:RNA, Small Interfering; D011384:Proinsulin; D005947:Glucose; D002118:Calcium