ATP-sensitive potassium channelopathies: focus on insulin secretion
Frances M. Ashcroft
Frances M. Ashcroft
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ATP-sensitive potassium channelopathies: focus on insulin secretion

Abstract

ATP-sensitive potassium (KATP) channels, so named because they are inhibited by intracellular ATP, play key physiological roles in many tissues. In pancreatic β cells, these channels regulate glucose-dependent insulin secretion and serve as the target for sulfonylurea drugs used to treat type 2 diabetes. This review focuses on insulin secretory disorders, such as congenital hyperinsulinemia and neonatal diabetes, that result from mutations in KATP channel genes. It also considers the extent to which defective regulation of KATP channel activity contributes to the etiology of type 2 diabetes.

Authors

Frances M. Ashcroft

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Figure 5

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Effects of Kir6.2 mutations on channel gating. (A) Schematic of the diff...
Effects of Kir6.2 mutations on channel gating. (A) Schematic of the different channel types expected when WT and mutant Kir6.2 are coexpressed (as in the heterozygous state). The box indicates channel types expected to have altered ATP sensitivity if the mutation affects channel gating (see text). (B) Single KATP channel currents recorded at –60 mV from inside-out patches from oocytes coinjected with mRNAs encoding SUR1 plus either WT or mutant Kir6.2 as indicated. Reproduced with permission from Proceedings of the National Academy of Sciences of the United States of America (83).