Diabetes, Vol 48, Issue 10 1971-1978, Copyright © 1999 by American Diabetes Association

ARTICLES

Mechanisms of coordination of Ca2+ signals in pancreatic islet cells

F Bertuzzi, AM Davalli, R Nano, C Socci, F Codazzi, R Fesce, V Di Carlo, G Pozza and F Grohovaz
Surgical Department, and Consiglio Nazionale delle Ricerche Cellular and Molecular Pharmacology Center, S. Raffaele Scientific Institute, Milan, Italy. bertuzzi.federico@hsr.it

Within pancreatic islet cells, rhythmic changes in the cytosolic Ca2+ concentration have been reported to occur in response to stimulatory glucose concentrations and to be synchronous with pulsatile release of insulin. We explored the possible mechanisms responsible for Ca2+ signal propagation within islet cells, with particular regard to gap junction communication, the pathway widely credited with being responsible for coordination of the secretory activity. Using fura-2 imaging, we found that multiple mechanisms control Ca2+ signaling in pancreatic islet cells. Gap junction blockade by 18 alpha-glycyrrhetinic acid greatly restricted the propagation of Ca2+ waves induced by mechanical stimulation of cells but affected neither Ca2+ signals nor insulin secretion elicited by glucose elevation. The source of Ca2+ elevation was also different under the two experimental conditions, the first being sustained by release from inner stores and the second by nifedipine-sensitive Ca2+ influx. Furthermore, glucose-induced Ca2+ waves were able to propagate across cell-free clefts, indicating that diffusible factors can control Ca2+ signal coordination. Our results provide evidence that multiple mechanisms of Ca2+ signaling operate in beta-cells and that gap junctions are not required for intercellular Ca2+ wave propagation or insulin secretion in response to glucose.
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