Insulin signalling through ultradian oscillations

Abstract

Periodic oscillations appear to be a characteristic of insulin secretion at various different levels. Very rapid pulsations are seen in the isolated beta-cell and islet, while rapid (10- to 15-min) pulsations are seen both in the intact organism and in the isolated pancreas. Ultradian oscillations, particularly evident in situations of sustained exogenous glucose loading, appear to be a characteristic of intact organisms and have been hypothesized to be intrinsic to the normal glucose-insulin feedback system. Many of the features seen in experimental situations and in abnormalities of the system can be predicted by computer modelling of this system, supporting this hypothesis. A further theoretical feature of this hypothesis, borne out by experiment, is the ability to entrain insulin pulsatility by oscillations in an exogenous glucose infusion. Identification of defective ultradian oscillations and entrainment can identify subtle abnormalities of insulin sensitivity and pancreatic function, and restoration of normal function can be demonstrated after pharmaceutical intervention.