Intracellular MgADP may regulate insulin secretion by binding to SUR NBF2 and antagonizing ATP inhibition of KATP channels, as demonstrated by mutations causing hyperinsulinemic hypoglycemia.
Intracellular MgADP regulates insulin secretion by binding to SUR NBF2 and antagonizing ATP inhibition of KATP channels.
Adenosine triphosphate (ATP)-sensitive potassium (KATP) channels couple the cellular metabolic state to electrical activity and are a critical link between blood glucose concentration and pancreatic insulin secretion. A mutation in the second nucleotide-binding fold (NBF2) of the sulfonylurea receptor (SUR) of an individual diagnosed with persistent hyperinsulinemic hypoglycemia of infancy generated KATP channels that could be opened by diazoxide but not in response to metabolic inhibition. The hamster SUR, containing the analogous mutation, had normal ATP sensitivity, but unlike wild-type channels, inhibition by ATP was not antagonized by adenosine diphosphate (ADP). Additional mutations in NBF2 resulted in the same phenotype, whereas an equivalent mutation in NBF1 showed normal sensitivity to MgADP. Thus, by binding to SUR NBF2 and antagonizing ATP inhibition of KATP++ channels, intracellular MgADP may regulate insulin secretion.
Nichols et al. (Fri,) conducted a other in Persistent hyperinsulinemic hypoglycemia of infancy. Mutation in the second nucleotide-binding fold (NBF2) of the sulfonylurea receptor (SUR) vs. Wild-type channels was evaluated on KATP channel response to metabolic inhibition and ATP sensitivity. Intracellular MgADP may regulate insulin secretion by binding to SUR NBF2 and antagonizing ATP inhibition of KATP channels, as demonstrated by mutations causing hyperinsulinemic hypoglycemia.