Insulin granule trafficking in beta-cells: mathematical model of glucose-induced insulin secretion

Am J Physiol Endocrinol Metab. 2007 Jul;293(1):E396-409. doi: 10.1152/ajpendo.00647.2006. Epub 2007 Apr 24.

Abstract

A mathematical model that represents the dynamics of intracellular insulin granules in beta-cells is proposed. Granule translocation and exocytosis are controlled by signals assumed to be essentially related to ATP-to-ADP ratio and cytosolic Ca(2+) concentration. The model provides an interpretation of the roles of the triggering and amplifying pathways of glucose-stimulated insulin secretion. Values of most of the model parameters were inferred from available experimental data. The numerical simulations represent a variety of experimental conditions, such as the stimulation by high K(+) and by different time courses of extracellular glucose, and the predicted responses agree with published experimental data. Model capacity to represent data measured in a hyperglycemic clamp was also tested. Model parameter changes that may reflect alterations of beta-cell function present in type 2 diabetes are investigated, and the action of pharmacological agents that bind to sulfonylurea receptors is simulated.

Publication types

  • Evaluation Study

MeSH terms

  • Animals
  • C-Peptide / metabolism
  • Computer Simulation
  • Glucose / pharmacology*
  • Glucose Clamp Technique
  • Humans
  • Insulin / metabolism*
  • Insulin Secretion
  • Insulin-Secreting Cells / drug effects*
  • Insulin-Secreting Cells / metabolism*
  • Models, Biological
  • Models, Theoretical*
  • Secretory Vesicles / drug effects
  • Secretory Vesicles / metabolism*

Substances

  • C-Peptide
  • Insulin
  • Glucose