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Dual Effect of Cell-Cell Contact Disruption on Cytosolic Calcium and Insulin Secretion

Department of Genetic Medicine and Development (F.J., A.T., A.-L.P., J.-C.I., P.A.H.) and Department of Cell Physiology and Metabolism (H.J., C.B.W., N.D.), University of Geneva Medical Center, 1211 Geneva-4, Switzerland

Address all correspondence and requests for reprints to: Fabienne Jaques, Department of Genetic Medicine and Development, University of Geneva Medical Center, 1211 Geneva-4, Switzerland. E-mail: fabienne.jaques{at}medecine.unige.ch.

Cell-to-cell interactions play an important role in insulin secretion. Compared with intact islets, dispersed pancreatic β-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 Ca²⁺ activity, depolymerized cytoskeleton and ERK1/2 activation in low glucose conditions. Both the increased basal secretion and the spontaneous Ca²⁺ activity were corrected by transient removal of Ca²⁺ 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 β-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 Ca²⁺ transients that activate downstream Ca²⁺ 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.