Mechanisms of coordination of Ca2+ signals in pancreatic islet cells

Within pancreatic islet cells, rhythmic changes in the cytosolic Ca2+ conce ntration have been reported to occur in response to stimulatory glucose con centrations and to be synchronous with pulsatile release of insulin. We exp lored the possible mechanisms responsible for Ca2+ signal propagation withi n islet cells, with particular regard to gap junction communication, the pa thway widely credited with being responsible for coordination of the secret ory activity. Using fura-2 imaging, we found that multiple mechanisms contr ol Ca2+ signaling in pancreatic islet cells. Gap junction blockade by 18 al pha-glycyrrhetinic acid greatly restricted the propagation of Ca2+ waves in duced by mechanical stimulation of cells but affected neither Ca2+ signals nor insulin secretion elicited by glucose elevation. The source of Ca2+ ele vation was also different under the two experimental conditions, the first being sustained by release from inner stores and the second by nifedipine-s ensitive Ca2+ influx. Furthermore, glucose-induced Ca2+ waves were able to propagate across cell-free clefts, indicating that diffusible factors can c ontrol 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 secreti on in response to glucose.