A new biphasic minimal model.

Plasma insulin levels vary in an oscillatory fashion in both basal and postprandial states. The basic pattern is one of rapid (10 min) pulses superimposed on slower (50-100 min) oscillations. These oscillations increase after a glucose load and are altered in type 2 diabetes, impaired glucose tolerance or ageing. In response to a square-wave increase in interstitial glucose, beta-cells release insulin in a biphasic manner, with a sharp first phase lasting approximately 10 min followed by a gradually increasing release (second phase). Both phases are important for maintaining glucose homeostasis, but more emphasis has been placed on early insulin release because its attenuation causes glucose intolerance and late hyperinsulinemia. A new minimal model of glucose and insulin concentrations in plasma, which incorporates both the pulsatile and biphasic aspect of insulin production into existing minimal models, has been developed. The model is founded upon recent results on the action of beta-cells as fuel sensors and the dynamics of secretory granule exocytosis. The inclusion of a flexible model of insulin release is essential if the model is to be used to describe diabetic patients for more than a few hours and is a step towards a 24 hour free living model.