Update of variants identified in the pancreatic beta‐cell K ATP channel genes KCNJ11 and ABCC8 in individuals with congenital hyperinsulinism and diabetes

Abstract

The most common genetic cause of neonatal diabetes and hyperinsulinism are pathogenic variants in ABCC8 and KCNJ11. These genes encode the subunits of the beta‐cell ATP sensitive potassium channel, a key component of the glucose‐stimulated insulin secretion pathway. Mutations in the two genes cause dysregulated insulin secretion; inactivating mutations cause an over‐secretion of insulin leading to congenital hyperinsulinism, whilst activating mutations cause the opposing phenotype, diabetes. This review focuses on variants identified in ABCC8 and KCNJ11, the phenotypic spectrum and the treatment implications for individuals with pathogenic variants.