Mathematical modeling of insulin secretion and the role of glucose-dependent mobilization, docking, priming and fusion of insulin granules

► We developed a new mathematical model of glucose-stimulated insulin secretion. ► The model reproduces results from multiple experimental systems. ► The staircase experiment can be explained without introducing β-cell heterogeneity. ► Insulin secretion dynamics depend on a graded response to glucose by β-cells. ► Rate of granule mobilization is a critical limiting factor of second phase insulin release.