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

Prost, Anne-Lise
Published in Endocrinology. 2008, vol. 149, no. 5, p. 2494-505
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.
Keywords AnimalsCadherins/antagonists & inhibitors/metabolismCalcium/metabolismCalcium Channels/metabolism/physiologyCell Adhesion/drug effects/geneticsCell Communication/physiologyCell Proliferation/drug effectsCells CulturedContact Inhibition/physiologyCytosol/metabolismDown-Regulation/drug effectsGlucose/pharmacologyInsulin/secretionInsulin-Secreting Cells/drug effects/metabolism/physiology/secretionMiceOligonucleotide Array Sequence AnalysisProinsulin/metabolismProtein TransportRNA Small Interfering/pharmacology
PMID: 18218692
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Research groups Signaux intracellulaires (210)
Fonction de l'îlot de Langerhans (324)
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JAQUES, Fabienne et al. Dual effect of cell-cell contact disruption on cytosolic calcium and insulin secretion. In: Endocrinology, 2008, vol. 149, n° 5, p. 2494-505. https://archive-ouverte.unige.ch/unige:755

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Deposited on : 2009-02-11

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