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

Insulin is released from pancreatic β-cells as a result of Ca2+-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 Ca2+-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 β-cells. We then review mathematical models of granule dynamics and exocytosis in rodent β-cells and present a mathematical description of Ca2+-evoked exocytosis in human β-cells, which show clear differences to their rodent counterparts. The model suggests that L- and P/Q-type Ca2+-channels are involved to a similar degree in exocytosis during electrical activity in human β-cells.