Adenosine diphosphate as an intracellular regulator of insulin secretion

C. G. Nichols, S. L. Shyng, A. Nestorowicz, B. Glaser, J. P. Clement IV, G. Gonzalez, L. Aguilar-Bryan, M. A. Permutt, J. Bryan

Research output: Contribution to journalArticlepeer-review

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Adenosine triphosphate (ATP)-sensitive potassium (K(ATP)) 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 K(ATP) 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 K(ATP) channels, intracellular MgADP may regulate insulin secretion.

Original languageEnglish
Pages (from-to)1785-1787
Number of pages3
Issue number5269
StatePublished - Jun 21 1996


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