ANALYSIS OF POSSIBLE MECHANISMS FOR IN-VITRO OSCILLATIONS OF INSULIN-SECRETION

We explore possible kinetic mechanisms responsible for the oscillatory (pulsatile) secretion of insulin observed in vitro when pancreatic is lets or islet-derived cells are perifused with glucose. Three primary processes are included: 1) glucose stimulation of insulin secretion, c ontrolled by glucokinase; 2) uptake of glucose through GLUT transporte rs; and 3) glucose metabolism. Perifusion is approximated as a Limitin g case of a chemical flow reactor. Using experimentally determined rat e laws for the three processes, we examine the effects of exogenous in sulin as a phenomenological activator and inhibitor of secretion. The resulting differential equations support oscillations using either dir ect or indirect inhibition by insulin. The oscillations have many of t he characteristics observed in vitro, although the indirect model is i n better overall agreement with experiment. We conclude that the mecha nisms explored here may help explain insulin oscillations for HIT cell s, but not for islets, and predict that oscillations can be modulated by including insulin in the perifusion medium.