Potassium channels, sulphonylurea receptors and control of insulin release

Clinical profiles of the glucose regulation disorders persistent hyperinsul inaemic hypoglycaemia of infancy (PHHI) and diabetes mellitus are diametric ally opposed: unregulated insulin secretion versus insulin insufficiency. Y et, despite this, recent studies of PHHI and other rare neonatal conditions have revealed common pathways of cellular dysfunction relevant to our unde rstanding of diabetes. Such work has been based upon integration of the gen etics of these diseases with the cellular and molecular biology of a potass ium channel known to play a major role in the 'glucose-sensing apparatus' o f the pancreatic beta cell - the ATP-sensitive K+ (K-ATP) channel. The stru cture 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 cassett e protein that has an extraordinarily high affinity for sulphonylurea compo unds. Here, we describe how defects in K-ATP channel genes give rise to ins ulin hypersecretion, and may also predispose to the onset of Type 2 diabete s, and how acquired losses of function of these channels have been implicat ed in maturity onset diabetes of the young and reactive hyperinsulinaemia-i nduced hypoglycaemia.