Neonatal Diabetes and the KATP Channel: From Mutation to Therapy

Activating mutations in one of the two subunits of the ATP-sensitive potassium (K-ATP) channel cause neonatal diabetes (ND). This may be either transient or permanent and, in approximately 20% of patients, is associated with neuro-developmental delay. In most patients, switching from insulin to oral sulfonylurea therapy improves glycemic control and ameliorates some of the neurological disabilities. Here, we review how K-ATP channel mutations lead to the varied clinical phenotype, how sulfonylureas exert their therapeutic effects, and why their efficacy varies with individual mutations.