High-Dose Glibenclamide Can Replace Insulin Therapy Despite Transitory Diarrhea in Early-Onset Diabetes Caused by a Novel R201L Kir6.2 Mutation

Recently, mutations in the gene KCNJ11 encoding the Kir 6.2 subunit of the ATP-sensitive K+ channel (KATP channel) have been described in patients with permanent neonatal diabetes (1). The KATP channel complex is an aggregate of four subunits of the Kir6.2 inward rectifier channel plus four regulatory units known as the sulfonylurea receptor (SUR1). In pancreatic β-cells, glucose metabolism leads to a rapid rise in intracellular ATP levels, leading to closure of the KATP channel. The resultant cell depolarization is critical for normal insulin secretion. Sulfonylureas are able to close the KATP channel by interacting with SUR1 via an ATP-independent mechanism. As a result, four young patients carrying mutations in the Kir6.2 channel have been treated with sulfonylureas (2,3) and withdrawn from insulin. To test whether …