MATHEMATICAL-ANALYSIS OF A PROPOSED MECHANISM FOR OSCILLATORY INSULIN-SECRETION IN PERIFUSED HIT-15 CELLS

Oscillatory secretion of insulin has been observed in many different e xperimental preparations ranging from pancreatic islets to the whole p ancreas. Here we examine the mathematical features underlying a possib le model for oscillatory secretion from the perifused, insulin-secreti ng cell line, HIT-15. The model includes the kinetics of uptake of glu cose by GLUT transporters, the rate of glucose metabolism within the c ell, and the effect of glucose on the rate of insulin secretion. Putat ive feedback by insulin on the rate of glucose transport into the cell s is treated phenomenologically and leads to insulin oscillations simi lar to those observed experimentally in HIT cells. The resulting set o f 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 characteristi cs of the oscillations and their sensitivity to parameter variation us ing phase plane analysis.