Oscillations of secretion driven by oscillations of cytoplasmic Ca2+ as evidences in single pancreatic islets

It is often assumed, but has not been demonstrated, that the oscillations of cytoplasmic calcium (Ca2+i) that occur in various secretory cells induce oscillations in secretion. Here, we have used single pancreatic islets from normal mice to monitor simultaneously insulin release and Ca2+i in beta-cells for periods up to 25 min. Ca2+i and insulin secretion were found to oscillate in synchrony during stimulation by glucose. This synchrony persisted when the frequency of both events changed spontaneously or upon addition of the hypoglycaemic sulfonylurea tolbutamide, or when their relative amplitudes varied. Repolarizing the beta-cell membrane with diazoxide abolished both Ca2+i and insulin oscillations. In contrast, epinephrine suppressed insulin oscillations in spite of the persistence of Ca2+i oscillations. This study is the first direct demonstration that, in an intact organ, sustained oscillations of Ca2+i induced by a physiological stimulus entrain synchronous oscillations of the functional response, and that both events can vary simultaneously or be dissociated depending on the experimental conditions.