Sulfonylureas are important drugs used for treatment of diabetes that act through adenosine triphosphate–sensitive potassium channels to promote secretion of insulin from the pancreas. Zhang et al. present another mechanism by which the beneficial effects of sulfonylureas may also be obtained. Sulfonylureas were identified in a screen for substances that modify the activity of Epac2, a guanine nucleotide exchange factor for the small guanosine triphosphatase Rap1. Mice lacking Epac2 were less responsive to sulfonylureas, which may suggest that Epac2 would be a useful target for development of drugs for treatment of diabetes.
C.-L. Zhang, M. Katoh, T. Shibasaki, K. Minami, Y. Sunaga, H. Takahashi, N. Yokoi, M. Iwasaki, T. Miki, S. Seino, The cAMP sensor Epac2 is a direct target of antidiabetic sulfonylurea drugs. Science 325, 607–610 (2009).[Abstract] [Full Text]