Metabolic and electrical oscillations: partners in controlling pulsatile insulin secretion

Impairment of insulin secretion from the beta-cells of the pancreatic islets of Langerhans is central to the development of type 2 diabetes mellitus and has therefore been the subject of much investigation. Great advances have been made in this area, but the mechanisms underlying the pulsatility of insulin secretion remain controversial. The period of these pulses is 4 - 6 min and reflects oscillations in islet membrane potential and intracellular free Ca2+. Pulsatile blood insulin levels appear to play an important physiological role in insulin action and are lost in patients with type 2 diabetes and their near relatives. We present evidence for a recently developed beta-cell model, the "dual oscillator model," in which oscillations in activity are due to both electrical and metabolic mechanisms. This model is capable of explaining much of the available data on islet activity and offers possible resolutions of a number of longstanding issues. The model, however, still lacks direct confirmation and raises new issues. In this article, we highlight both the successes of the model and the challenges that it poses for the field.