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

Objective Because children with congenital hyperinsulinism (HI) caused by recessive loss of function mutations in the adenosine triphosphate (ATP)-dependent potassium channel (K-ATP-HI) are not leucine sensitive, we evaluated for protein-induced hypoglycemia with oral protein tolerance tests. Study design Blood glucose and insulin concentrations were measured every 15 minutes for 3 hours after an oral protein load in children with K-ATP-HI (n = 11) and compared with those of children with glutamate dehydrogenase HI (n = 12) and control subjects (n = 12). Results Similar to children with glutamate dehydrogenase HI, patients with k(ATP)-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. Conclusions Protein-induced hypoglycemia is a feature of K-ATP-HI, despite the absence of leucine sensitivity. The results indicate that amino acids can stimulate insulin secretion via a glutamate dehydrogenase- and K-ATP channel-independent pathway.