Abstract
Sulfonylureas (SU), commonly used in the treatment of type 2 diabetes mellitus (T2DM), stimulate insulin secretion by inhibiting adenosine triphosphate (ATP)‐sensitive K
+
(K
ATP
) channels in pancreatic β‐cells. SU are now known to also activate cyclic adenosine monophosphate (cAMP) sensor Epac2 (cAMP‐GEFII) to Rap1 signaling, which promotes insulin secretion. The different effects of various SU on Epac2/Rap1 signaling, as well as K
ATP
channels in different tissues, underlie the diverse pancreatic and extra‐pancreatic actions of SU.
(J Diabetes Invest, doi: 10.1111/j.2040‐1124.2010.00014.x, 2010)