Mathematical analysis of a proposed mechanism for oscillatory insulin secretion in perifused HIT-15 cells

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Abstract
Oscillatory secretion of insulin has been observed in many different experimental preparations ranging from pancreatic islets to the whole pancreas. Here we examine the mathematical features underlying a possible model for oscillatory secretion from the perifused, insulin-secreting cell line, HIT-15. The model includes the kinetics of uptake of glucose by GLUT transporters, the rate of glucose metabolism within the cell, and the effect of glucose on the rate of insulin secretion. Putative feedback by insulin on the rate of glucose transport into the cells is treated phenomenologically and leads to insulin oscillations similar to those observed experimentally in HIT cells. The resulting set of ordinary differential equations is simplified by time-scale analysis to a two-variable set of ordinary differential equations. Because of this simplification we can explore, in great detail, the characteristics of the oscillations and their sensitivity to parameter variation using phase plane analysis.