Mechanisms of coordination of Ca2+ signals in pancreatic islet cells

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 α-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 β-cells and that gap junctions are not required for intercellular Ca²⁺ wave propagation or insulin secretion in response to glucose.