Pancreatic cell K⁺ATP channels

Abstract

Sulphonylureas have been the backbone of the management of type 2 diabetes mellitus. As they interact with pancreatic beta cell KATP channels in islets of Langerhans and stimulate insulin secretion, the ^KATP channel has recently become a focus of attention of scientists. The beta cell ^KATP channel is composed of Kir 6.2 / SUR1, in which the channel pore is formed by Kir 6.2. Although four ATP binding sites lie on the Kir 6.2, binding with one site is sufficient for channel closure. ATP inhibits the channel by interacting with Kir 6.2, while sulphonylurea blocks the channel activity by interaction with high affinity binding site on SUR1 and a low affinity site on Kir 6.2 suggesting a bivalent binding site for some sulphonylureas (e.g. glibenclamide). By cloning techniques, cDNA structure, gene structure and promoter sequences of SUR1 and Kir 6.2 have been studied in great detail and some diseases have been linked to mutations in the ^KATP channels. Better understanding of ^KATP channels could potentially help to develop newer therapeutic molecules that are safer, more effective and hopefully could prevent secondary failure to these agents in the future.