Molecular Defects of ATP-Sensitive Potassium Channels in Congenital Hyperinsulinism

The beta-cell ATP-sensitive potassium (KATP) channel plays a key role in regulating insulin secretion by linking glucose metabolism to cell excitability. The channel is a protein complex composed of four Kir6.2 inwardly rectifying potassium channel subunits and four sulfonylurea receptor 1 subunits encoded by KCNJ11 and ABCC8, respectively. KATP channel function in beta-cells is dependent on correct expression as well as proper gating of the channel by metabolic signals at the plasma membrane. Mutations in ABCC8 or KCNJ11 that perturb channel expression or gating can reduce channel function and lead to congenital hyperinsulinism. This chapter reviews recent advances in understanding the pathophysiology of mutant KATP channels from in vitro functional studies.