In Vitro Recovery of ATP-Sensitive Potassium Channels in b-Cells From Patients With Congenital Hyperinsulinism of Infancy

OBJECTIVE—Congenital hyperinsulinism in infancy (CHI) is characterized by unregulated insulin secretion from pancreatic b-cells; severe forms are associated with defects in ABCC8 and KCNJ11 genes encoding sulfonylurea receptor 1 (SUR1) and Kir6.2 subunits, which form ATP-sensitive K+ (KATP) channels in b-cells. Diazoxide therapy often fails in the treatment of CHI and may be a result of reduced cell surface expression of KATP channels. We hypothesized that conditions known to facilitate trafficking of cystic fibrosis transmembrane regulator (CFTR) and other proteins in recombinant expression systems might in-crease surface expression of KATP channels in native CHI b-cells. RESEARCH DESIGN AND METHODS—Tissue was isolated during pancreatectomy from eight patients with CHI and from adult cadaver organ donors. Patients were screened for muta-tions in ABCC8 and KCNJ11. Isolated b-cells were maintained a