Protein-sensitive hypoglycemia without leucine sensitivity in hyperinsulinism caused by K_ATP 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.

Abbreviations:  ATP, Adenosine triphosphate , BG, Blood glucose concentration , GDH, Glutamate dehydrogenase , HI, Hyperinsulinism , K_ATP, Adenosine triphosphate-dependent potassium channel , Kir6.2, Potassium ion pore , OPTT, Oral protein tolerance test , SUR1, Sulfonylurea receptor