, Volume 460, Issue 2, pp 307-320
Date: 18 Nov 2009

KATP channelopathies in the pancreas

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Abstract

Adenosine-triphosphate-sensitive potassium channels (KATP) are regulated by adenosine nucleotides, and, thereby, couple cellular metabolism with electrical activity in multiple tissues including the pancreatic β-cell. The critical involvement of KATP in insulin secretion is confirmed by the demonstration that inactivating and activating mutations in KATP underlie persistent hyperinsulinemia and neonatal diabetes mellitus, respectively, in both animal models and humans. In addition, a common variant in KATP represents a risk factor in the etiology of type 2 diabetes. This review focuses on the mechanistic basis by which KATP mutations underlie insulin secretory disorders and the implications of these findings for successful clinical intervention.