Mathematical modeling and statistical analysis of calcium-regulated insulin granule exocytosis in beta-cells from mice and humans.

Summary, in English

Insulin is released from pancreatic beta-cells as a result of Ca(2+)-evoked exocytosis of dense-core granules. Secretion is biphasic, which has been suggested to correspond to the release of different granule pools. Here we review and carefully reanalyze previously published patch-clamp data on depolarization-evoked Ca(2+)-currents and corresponding capacitance measurements. Using a statistical mixed-effects model, we show that the data indicate that pool depletion is negligible in response to short depolarizations in mouse beta-cells. We then review mathematical models of granule dynamics and exocytosis in rodent beta-cells and present a mathematical description of Ca(2+)-evoked exocytosis in human beta-cells, which show clear differences to their rodent counterparts. The model suggests that L- and P/Q-type Ca(2+)-channels are involved to a similar degree in exocytosis during electrical activity in human beta-cells.