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Treating diabetes today: a matter of selectivity of sulphonylureas
Author(s) -
Seino S.,
Takahashi H.,
Takahashi T.,
Shibasaki T.
Publication year - 2012
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/j.1463-1326.2011.01507.x
Subject(s) - exocytosis , insulin , sulfonylurea receptor , endocrinology , medicine , rap1 , chemistry , diabetes mellitus , guanine nucleotide exchange factor , metformin , incretin , microbiology and biotechnology , secretion , type 2 diabetes , pharmacology , signal transduction , biology , glibenclamide , biochemistry
It is well known that sulphonylureas (SUs), commonly used in the treatment of type 2 diabetes mellitus, stimulate insulin secretion by closing ATP‐sensitive K + (K ATP ) channels in pancreatic β ‐cells by binding to the SU receptor SUR1. SUs are now known also to activate cAMP sensor Epac2 (cAMP‐GEFII) to Rap1 signalling, which promotes insulin granule exocytosis. For SUs to exert their full effects in insulin secretion, they are required to activate Epac2 as well as to inhibit the β ‐cell K ATP channels. As Epac2 is also necessary for potentiation of glucose‐induced insulin secretion by cAMP‐increasing agents, such as incretin, Epac2 is a target of both cAMP and SUs. The distinct effects of various SUs appear to be because of their different actions on Epac2/Rap1 signalling as well as K ATP channels. Differently from other SUs, gliclazide is unique in that it is specific for β ‐cell K ATP channel and does not activate Epac2.