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Updated: May 27, 2026

Improving IV Insulin Administration in a Community Hospital
Published on: June 11, 2012
Treating diabetes today: a matter of selectivity of sulphonylureas
S Seino1, H Takahashi, T Takahashi
1Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Chuo-ku, Kobe, Japan. seino@med.kobe-u.ac.jp
Abstract:
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.
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