Catalyzing Diabetes Drug Discovery

Science's STKE  22 Jul 2003:
Vol. 2003, Issue 192, pp. tw287-TW287
DOI: 10.1126/stke.2003.192.tw287

One relatively unexplored drug target for type 2 diabetes is the glucose-sensing enzyme glucokinase (GK); mutations that reduce GK activity cause a rare inherited form of diabetes in humans. Grimsby et al. have identified a class of small molecules that allosterically activate GK. When orally administered to rodent models of type 2 diabetes, these compounds significantly improved glucose tolerance by enhancing glucose-dependent insulin secretion from the pancreas and by stimulating glucose utilization in the liver.

J. Grimsby, R. Sarabu, W. L. Corbett, N.-E. Haynes, F. T. Bizzarro, J. W. Coffey, K. R. Guertin, D. W. Hilliard, R. F. Kester, P. E. Mahaney, L. Marcus, L. Qi, C. L. Spence, J. Tengi, M. A. Magnuson, C. A. Chu, M. T. Dvorozniak, F. M. Matschinsky, J. F. Grippo, Allosteric activators of glucokinase: Potential role in diabetes therapy. Science 301, 370-373 (2003). [Abstract] [Full Text]