Of mice and men: K(ATP) channels and insulin secretion.

K(ATP) channels are a unique, small family of potassium (K+)-selective ion channels assembled from four inward rectifier pore-forming subunits, K(IR)6.x, paired with four sulfonylurea receptors (SURs), members of the adenosine triphosphate (ATP)-binding cassette superfamily. The activity of these channels can be regulated by metabolically driven changes in the ratio of adenosine diphosphate (ADP) to ATP, providing a means to couple membrane electrical activity with metabolism. In pancreatic beta cells in the islets of Langerhans, K(ATP) channels are part of an ionic mechanism that couples glucose metabolism to insulin secretion. This chapter 1) briefly describes the properties of K(ATP) channels; 2) discusses data on a genetically recessive form of persistent hyperinsulinemic hypoglycemia of infancy (PHHI), caused by loss of beta-cell K(ATP) channel activity; and 3) compares the severe impairment of glucose homeostasis that characterizes the human phenotype with the near-normal phenotype observed in K(ATP) channel null mice.