Abstract
Sulfonylureas (SU), commonly used in the treatment of type 2 diabetes mellitus (T2DM), stimulate insulin secretion by inhibiting adenosine triphosphate (ATP)-sensitive K(+) (KATP) 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 KATP 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).