Diabetes and insulin secretion:: whither KATP?

The critical involvement of ATP-sensitive potassium (K-ATP) channels in insulin secretion is confirmed both by the demonstration that mutations that reduce K-ATP channel activity underlie many if not most cases of persistent hyperinsulinemia, and by the ability of sulfonylureas, which inhibit K-ATP channels, to enhance insulin secretion in type II diabetics. By extrapolation, we contend that mutations that increase beta-cell K-ATP channel activity should inhibit glucose-dependent insulin secretion and underlie, or at least predispose to, a diabetic phenotype. In transgenic animal models, this prediction seems to be borne out. Although earlier genetic studies failed to demonstrate a linkage between K-ATP mutations and diabetes in humans, recent studies indicate significant association of K-ATP channel gene mutations or polymorphisms and type II diabetes. We suggest that further efforts to understand the involvement of K-ATP channels in diabetes are warranted.