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1 Institute of Systems Analysis and Computer Science, CNR, Rome, Italy
2 Department of Systems Analysis and Informatics, University of Rome ``La Sapienza'', Rome, Italy
3 Istituto di Clinica Medica, Università Cattolica S. Cuore, Rome, Italy
* To whom correspondence should be addressed. E-mail: gmingrone{at}rm.unicatt.it.
A mathematical model that represents the dynamics of intracellular insulin granules in
-cells is proposed. Granule translocation and exocytosis are controlled by signals assumed to be essentially related to ATP/ADP ratio and cytosolic Ca2+ 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
-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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