Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Sci. Signal., 25 August 2009
Vol. 2, Issue 85, p. pe54
Epac2: A Molecular Target for Sulfonylurea-Induced Insulin Release
Simon A. Hinke*
Department of Pharmacology, University of Washington, Box 357750, Seattle, WA 98195, USA.
Sulfonylurea drugs are used in type 2 diabetes mellitus therapy to induce release of endogenous insulin from pancreatic β cells. They act on sulfonylurea receptors, which are the regulatory subunits of adenosine triphosphate (ATP)–sensitive potassium ion (KATP) channels and cause channel closure to trigger exocytosis. Epac2 was identified as an intracellular target for sulfonylurea drugs, providing a potential nonelectrogenic signaling component to the mechanism of action for these agents. Commonly used sulfonylureas such as tolbutamide and glibenclamide induced Epac2 activation with distinct kinetic profiles. Epac2–/– mice failed to respond to sulfonylureas, suggesting that both sulfonylurea receptors and Epac2 are necessary for the action of these drugs. These data require that the cellular and physiological effects of drugs that alter the open state of the KATP channel be reassessed.