Abstract：
:Sulfonylureas and glinides are commonly used oral insulin secretagogues (ISs) that act on the pancreatic ATP-sensitive potassium (KATP) channel to promote insulin secretion in order to lower the blood glucose level. Physiologically, KATP channels are inhibited by intracellular ATP and activated by Mg-ADP. Therefore, they sense the cellular energy status to regulate the permeability of potassium ions across the plasma membrane. The pancreatic KATP channel is composed of the pore-forming Kir6.2 subunits and the regulatory SUR1 subunits. Previous electrophysiological studies have established that ISs bind to the SUR1 subunit and inhibit the channel activity primarily by two mechanisms. First, ISs prevent Mg-ADP activation. Second, ISs inhibit the channel activity of Kir6.2 directly. Several cryo-EM structures of the pancreatic KATP channel determined recently have provided remarkable structural insights into these two mechanisms.
journal_name
Biochemistryjournal_title
Biochemistryauthors
Wu JX,Ding D,Wang M,Chen Ldoi
10.1021/acs.biochem.9b00692subject
Has Abstractpub_date
2020-01-14 00:00:00pages
18-25issue
1eissn
0006-2960issn
1520-4995journal_volume
59pub_type
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