title: Mathematical modeling and statistical analysis of calcium-regulated insulin granule exocytosis in β-cells from mice and humans.
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.
authors.affiliation: 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
authors.forename: Morten Gram
authors.initials: MG
authors.lastname: Pedersen
authors.forename: Giuliana
authors.initials: G
authors.lastname: Cortese
authors.forename: Lena
authors.initials: L
authors.lastname: Eliasson
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D005089:Exocytosis; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D015203:Reproducibility of Results; D022142:Secretory Vesicles / Q000378:metabolism*
chemical_list: D007328:Insulin; D002118:Calcium