Abstract

ATP- sensitive potassium (KATP) channels are present in the surface membranes of many organs and cell types. In the pancreatic beta- cell, they play a critical role in coupling glucose metabolism to insulin secretion, and over the last few years, significant advances have been made in understanding the molecular basis of KATP channel activity, as well as the role of these channels in physiology and disease. KATP channels are generated from coassembly of Kir6.2 pore- forming subunits with sulfonylurea receptor 1 (SUR1) regulatory subunits. They are inhibited by intracellular ATP, and activated by ADP, so that glucose oxidation in beta- cells leads to a rise in [ATP]:[ADP] ratio, which reduces KATP channel activity and causes membrane depolarization. This leads to the opening of voltagedependent Ca2+ channels, elevated intracellular [Ca2+], and insulin exocytosis. Sulfonylureas, hypoglycemic agents used in the treatment of type 2 diabetes, act by binding to the regulatory SUR1 subunit and directly inhibiting the KATP current, bypassing metabolism to trigger insulin secretion. Conversely, KATP- specific channel openers (diazoxide) suppress insulin release by activating KATP and preventing a depolarization- dependent rise in intracellular [Ca2+]. Loss- of- function mutations in the genes (KCNJ11, ABCC8) that encode the two subunits (Kir6.2 and SUR1, respectively) of the KATP channel underlie hyperinsulinism that can in some cases be treated by potassium channel openers. This chapter will focus on advances in KATP channel biochemistry and physiology, and consider implications for future understanding of the mechanisms of control of insulin secretion in normal and diseased states.

Original languageEnglish
Title of host publicationMonogenic Hyperinsulinemic Hypoglycemia Disorders
PublisherS. Karger AG
Pages7-17
Number of pages11
Volume21
ISBN (Electronic)9783805599443
ISBN (Print)9783805599436
DOIs
StatePublished - Feb 16 2012

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    Remedi, M. S., & Nichols, C. G. (2012). Biochemistry and physiology of the ATP-sensitive potassium channel. In Monogenic Hyperinsulinemic Hypoglycemia Disorders (Vol. 21, pp. 7-17). S. Karger AG. https://doi.org/10.1159/000334464