Protein-sensitive hypoglycemia without leucine sensitivity in hyperinsulinism caused by KATP channel mutations

ObjectiveBecause children with congenital hyperinsulinism (HI) caused by recessive loss of function mutations in the adenosine triphosphate (ATP)-dependent potassium channel (KATP-HI) are not leucine sensitive, we evaluated for protein-induced hypoglycemia with oral protein tolerance tests.Study designBlood glucose and insulin concentrations were measured every 15 minutes for 3 hours after an oral protein load in children with KATP-HI (n = 11) and compared with those of children with glutamate dehydrogenase HI (n = 12) and control subjects (n = 12).ResultsSimilar to children with glutamate dehydrogenase HI, patients with KATP-HI displayed protein-induced hypoglycemia (10/11) with blood glucose concentrations declining by 17 to 69 mg/dL. In contrast, oral protein had little effect on blood glucose concentrations in control subjects.ConclusionsProtein-induced hypoglycemia is a feature of KATP-HI, despite the absence of leucine sensitivity. The results indicate that amino acids can stimulate insulin secretion via a glutamate dehydrogenase- and KATP channel-independent pathway.