title: Potassium Channels, Sulphonylurea Receptors and Control of Insulin Release.
abstract: Clinical profiles of the glucose regulation disorders persistent hyperinsulinaemic hypoglycaemia of infancy (PHHI) and diabetes mellitus are diametrically opposed: unregulated insulin secretion versus insulin insufficiency. Yet, despite this, recent studies of PHHI and other rare neonatal conditions have revealed common pathways of cellular dysfunction relevant to our understanding of diabetes. Such work has been based upon integration of the genetics of these diseases with the cellular and molecular biology of a potassium channel known to play a major role in the 'glucose-sensing apparatus' of the pancreatic beta cell - the ATP-sensitive K+ (KATP) channel. The structure of this protein complex is unique among ion channel families, because it is composed partly of a K+ channel and partly of an ATP-binding cassette protein that has an extraordinarily high affinity for sulphonylurea compounds. Here, we describe how defects in KATP channel genes give rise to insulin hypersecretion, and may also predispose to the onset of Type 2 diabetes, and how acquired losses of function of these channels have been implicated in maturity onset diabetes of the young and reactive hyperinsulinaemia-induced hypoglycaemia.