Of mice and men:: KATP 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.