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Prog Biophys Mol Biol. 2011 Nov;107(2):257-64. doi: 10.1016/j.pbiomolbio.2011.07.012. Epub 2011 Aug 4.

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

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1
Islet Cell Exocytosis, Lund University Diabetes Centre, Department of Clinical Sciences, Clinical Research Centre, Lund University, CRC 91-11, UMAS Entrance 72, SE-20502 Malmö, Sweden. morten_gram.pedersen@med.lu.se

Abstract

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.

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