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

      American Journal of Physiology - Endocrinology and Metabolism
      Animals, C-Peptide, secretion, Computer Simulation, Glucose, pharmacology, Glucose Clamp Technique, Humans, Insulin, metabolism, Insulin-Secreting Cells, drug effects, Models, Biological, Models, Theoretical, Secretory Vesicles

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          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.

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