Pulsatile insulin release: role of cytoplasmic Ca2+ oscillations.

Abstract

Oscillations of plasma insulin are essential for the hypoglycaemic effect of the hormone. Disturbance and partial loss of these oscillations occur during the development of Type 2 diabetes, in association with down-regulation of insulin receptors and insulin resistance. Oscillations with a frequency similar to that of plasma insulin have been observed in the cytoplasmic Ca2+ concentration ([Ca2+]i) of pancreatic beta cells, indicating that the ion plays a role in generating insulin pulses. Studies of individual islets have revealed that oscillations of [Ca2+]i and insulin release are synchronous. However, insulin release is also pulsatile under conditions in which [Ca2+]i is stable. These results support the notion that variations in the ATP/ADP ratio are sufficient to induce pulsatile insulin release. Under physiological conditions, this pulsatility may depend on the synergistic effects of ATP/ADP and [Ca2+]i oscillations.