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

TY - JOUR

T1 - Mathematical modeling and statistical analysis of calcium-regulated insulin granule exocytosis in ß-cells from mice and humans

AU - Pedersen, Morten Gram

AU - Cortese, Giuliana

AU - Eliasson, Lena

PY - 2011/11

Y1 - 2011/11

N2 - Insulin is released from pancreatic β-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 β-cells. We then review mathematical models of granule dynamics and exocytosis in rodent β-cells and present a mathematical description of Ca 2+-evoked exocytosis in human β-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 β-cells.

AB - Insulin is released from pancreatic β-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 β-cells. We then review mathematical models of granule dynamics and exocytosis in rodent β-cells and present a mathematical description of Ca 2+-evoked exocytosis in human β-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 β-cells.

U2 - 10.1016/j.pbiomolbio.2011.07.012

DO - 10.1016/j.pbiomolbio.2011.07.012

M3 - Journal article

C2 - 21839108

SN - 0079-6107

VL - 107

SP - 257

EP - 264

JO - Progress in Biophysics and Molecular Biology

JF - Progress in Biophysics and Molecular Biology

IS - 2

ER -