Distinct effects of glucose on the synchronous oscillations of insulin release and cytoplasmic Ca2+ concentration measured simultaneously in single mouse islets.

There exists a good temporal correlation between the oscillations of cytoplasmic Ca2+ ([Ca2+]i) in pancreatic B cells and insulin release. Here, single mouse islets loaded with fura-2 were used to investigate whether there also exists a quantitative correlation between both events during stimulation by different glucose concentrations. The frequency of [Ca2+]i oscillations was decreased by raising the CaCl2 concentration to 10 mM in the perifusion medium (to ensure adequate resolution of insulin oscillations by the immunoassay), and the glucose concentration was increased from 10 to 20 or from 15 to 30 mM. Raising the glucose level was followed by changes in [Ca2+]i oscillations. Their duration increased slightly, and that of the intervals decreased, whereas the nadir between the oscillations became less deep. On the other hand, the peak of [Ca2+]i oscillations did not change. As a result, the rhythm was accelerated, and the average [Ca2+]i was increased. The concomitant increase in insulin release resulted from similar changes, with, in addition, a marked increase in the peak of insulin oscillations. In two thirds of the islets, variations in the amplitude of successive [Ca2+]i oscillations occurred during stimulation with 10 mM glucose and disappeared at higher glucose levels. This was due to temporal variations in the responsiveness of all regions of the islet, rather than to the existence of nonresponsive regions that would be recruited into an active state by high glucose. In conclusion, there exists a good temporal correlation between insulin and [Ca2+]i oscillations in islets stimulated by various glucose concentrations. The quantitative correlation is not as close, indicating that the relationship between the two phenomena is nonlinear and supporting previous evidence that glucose also increases the efficacy of Ca2+ on secretion. This mechanism, rather than the development of a Ca2+ rise in nonresponsive cells, might underlie B cell recruitment in intact islets.