Mathematical modelling of stimulus-secretion coupling in the pancreatic B-cell. I. Dynamics of insulin release.

A mathematical model for cyclic AMP-Ca2+ interactions in pancreatic islets, defined in a previous study, was modified to include two new features. First, the cytosol and vacuolar Ca2+ pools were stratified in a cortical layer (representing 1 to 20% of the total cellular pool) and central core. Second, the changes in Ca2+ inflow and Ca2+ fractional outflow rate evoked by a rise in glucose concentration were discontinued during the 3rd and 4th min of stimulation. In this onion leaf sheet model, the biphasic pattern of glucose-induced insulin release could be simulated. This new model emphasizes the significance of both cytosol heterogeneity and signal discontinuity in the dynamics of insulin secretion.