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DDMODEL00000108: Chen’s exocytosis model

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Chen-Wang-Sherman’s model of Insulin Secretion by Kinetic Modeling of Granule Exocytosis
PharmML (0.6.1)
  • Identifying the targets of the amplifying pathway for insulin secretion in pancreatic beta-cells by kinetic modeling of granule exocytosis.
  • Chen YD, Wang S, Sherman A
  • Biophysical journal, 9/2008, Volume 95, Issue 5, pages: 2226-2241
  • Laboratory of Biological Modeling, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-5621, USA.
  • A kinetic model for insulin secretion in pancreatic beta-cells is adapted from a model for fast exocytosis in chromaffin cells. The fusion of primed granules with the plasma membrane is assumed to occur only in the "microdomain" near voltage-sensitive L-type Ca(2+)-channels, where [Ca(2+)] can reach micromolar levels. In contrast, resupply and priming of granules are assumed to depend on the cytosolic [Ca(2+)]. Adding a two-compartment model to handle the temporal distribution of Ca(2+) between the microdomain and the cytosol, we obtain a unified model that can generate both the fast granule fusion and the slow insulin secretion found experimentally in response to a step of membrane potential. The model can simulate the potentiation induced in islets by preincubation with glucose and the reduction in second-phase insulin secretion induced by blocking R-type Ca(2+)-channels (Ca(V)2.3). The model indicates that increased second-phase insulin secretion induced by the amplifying signal is controlled by the "resupply" step of the exocytosis cascade. In contrast, enhancement of priming is a good candidate for amplification of first-phase secretion by glucose, cyclic adenosine 3':5'-cyclic monophosphate, and protein kinase C. Finally, insulin secretion is enhanced when the amplifying signal oscillates in phase with the triggering Ca(2+)-signal.
Roberto Bizzotto
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  • Model owner: Roberto Bizzotto
  • Submitted: Dec 11, 2015 7:49:33 PM
  • Last Modified: May 18, 2016 3:18:44 PM
Revisions
  • Version: 15 public model Download this version
    • Submitted on: May 18, 2016 3:18:44 PM
    • Submitted by: Roberto Bizzotto
    • With comment: Edited model metadata online.
  • Version: 11 public model Download this version
    • Submitted on: May 18, 2016 3:04:49 PM
    • Submitted by: Roberto Bizzotto
    • With comment: Edited model metadata online.
  • Version: 9 public model Download this version
    • Submitted on: May 18, 2016 2:54:05 PM
    • Submitted by: Roberto Bizzotto
    • With comment: Updated model annotations.
  • Version: 6 public model Download this version
    • Submitted on: Dec 11, 2015 7:49:33 PM
    • Submitted by: Roberto Bizzotto
    • With comment: Edited model metadata online.
 
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