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

¹Institute of Systems Analysis and Computer Science, Consiglio Nazionale delle Ricerche, Rome; ²Department of Systems Analysis and Informatics, University of Rome "La Sapienza," Rome; and ³Institute of Internal Medicine, Catholic University School of Medicine, Rome, Italy

Submitted 27 November 2006 ; accepted in final form 16 April 2007

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-to-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.

-cell; insulin secretion; insulin granule dynamics; type 2 diabetes

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				M. G. Pedersen, A. Corradin, G. M Toffolo, and C. Cobelli A subcellular model of glucose-stimulated pancreatic insulin secretion Phil Trans R Soc A, October 13, 2008; 366(1880): 3525 - 3543. [Abstract] [Full Text] [PDF]