Stimulatory concentrations of glucose induce two patterns of [Ca²⁺]_c oscillations in mouse islets: simple or mixed in which rapid oscillations are superimposed on slow ones. The role of the membrane potential in the mixed pattern and the impact of this pattern on insulin release were studied here. Simultaneous measurements of [Ca²⁺]_c and insulin release from single islets revealed that mixed [Ca²⁺]_c oscillations triggered synchronous oscillations of insulin secretion. Simultaneous recordings of membrane potential in a single -cell within an islet and of [Ca²⁺]_c in the whole islet demonstrated that the mixed pattern results from compound bursting (i.e. clusters of membrane potential oscillations separated by prolonged silent intervals) that is synchronized in most -cells of the islet. Each slow [Ca²⁺]_c increase during mixed oscillations is due to a progressive summation of rapid oscillations. Digital image analysis confirmed the good synchrony between subregions of an islet. By contrast, islets from SERCA3 knock-out mice (SERCA3^-/-) did not display typical mixed [Ca²⁺]_c oscillations in response to glucose. This results from a lack of progressive summation of rapid oscillations and from an altered spontaneous electrical activity, i.e. lack of compound bursting, and membrane potential oscillations characterized by a lower frequency but larger depolarization phases than in SERCA3^+/+ -cells. In conclusion, glucose-induced mixed [Ca²⁺]_c oscillations result from compound bursting in all -cells of the islet. Disruption of SERCA3 abolishes mixed [Ca²⁺]_c oscillations, and augments -cell depolarization. This latter observation indicates that the endoplasmic reticulum participates in the control of the -cell membrane potential during glucose stimulation.