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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Calcium Signaling / physiology*
  • Exocytosis*
  • Humans
  • Insulin / metabolism*
  • Insulin Secretion
  • Insulin-Secreting Cells / cytology*
  • Insulin-Secreting Cells / metabolism*
  • Mice
  • Models, Biological*
  • Reproducibility of Results
  • Secretory Vesicles / metabolism*

Substances

  • Insulin
  • Calcium