Ionic and Metabolic Mechanisms in Pulsatile Insulin Secretion

Insulin is secreted in pulses with a period of about 5 minutes from the beta-cells of the pancreas. These pulses are in turn driven by oscillations of cytosolic calcium. Two parallel streams of investigation over more than two decades have studied metabolic oscillations and ionic mechanisms as possible sources of the calcium oscillations. We propose that the two are linked by a potassium channel, K(ATP), that senses the ATP and ADP levels in the cell. This directly transduces metabolic oscillations into oscillations of membrane potential and calcium. However, calcium can also affect metabolism by stimulating ATP-consuming pumps, by depolarizing the mitochondria, and by directly activating Krebs cycle enzymes. A unified model that combines the above elements and can thereby explain a diverse set of experimental observations using only a few simple assumptions will be presented