PHARMACOLOGY Catalyzing Diabetes Drug Discovery

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]

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Allosteric Activators of Glucokinase: Potential Role in Diabetes Therapy

Joseph Grimsby, Ramakanth Sarabu, Wendy L. Corbett, Nancy-Ellen Haynes, Fred T. Bizzarro, John W. Coffey, Kevin R. Guertin, Darryl W. Hilliard, Robert F. Kester, Paige E. Mahaney, Linda Marcus, Lida Qi, Cheryl L. Spence, John Tengi, Mark A. Magnuson, Chang An Chu, Mark T. Dvorozniak, Franz M. Matschinsky, and Joseph F. Grippo (18 July 2003)
Science 301 (5631), 370. [DOI: 10.1126/science.1084073]
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