Calcium and Metabolic Oscillations in Pancreatic Islets: Who's Driving the Bus?
Margaret Watts, Bernard Fendler, Matthew J. Merrins, Leslie S. Satin, Richard Bertram, Arthur Sherman
Pancreatic islets exhibit bursting oscillations in response to elevated blood glucose. These oscillations are accompanied by oscillations in the free cytosolic calcium concentration (Cac), which drives pulses of insulin secretion. Both islet calcium and metabolism oscillate, but there is some debate about their interrelationship. Recent experimental data show that metabolic oscillations in some cases persist after the addition of diazoxide (Dz), which opens K(ATP) channels, hyperpolarizing beta-cells and preventing calcium entry and calcium oscillations. Further, in some islets in which metabolic oscillations were eliminated with Dz, increasing the cytosolic calcium concentration by the addition of KCl could restart the metabolic oscillations. Here we address why metabolic oscillations persist in some islets but not others, and why raising Cac restarts oscillations in some islets but not others. We answer these questions using the dual oscillator model (DOM) for pancreatic islets. The DOM can reproduce the experimental data and shows that the model supports two different mechanisms for slow metabolic oscillations, one that requires calcium oscillations and one that does not.