Insulin granule trafficking in beta-cells: mathematical model of glucose-induced insulin secretion.
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.
Bertuzzi
Alessandro
A
Institute of Systems Analysis and Computer Science, Consiglio Nazionale delle Ricerche, Rome.
Salinari
Serenella
S
Mingrone
Geltrude
G
D000818:Animals; D002096:C-Peptide / Q000378:metabolism; D003198:Computer Simulation; D005947:Glucose / Q000494:pharmacology*; D015309:Glucose Clamp Technique; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism*; D008954:Models, Biological; D008962:Models, Theoretical; D022142:Secretory Vesicles / Q000187:drug effects / Q000378:metabolism*
D002096:C-Peptide; D007328:Insulin; D005947:Glucose