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Allosteric Activators of Glucokinase: Potential Role in Diabetes Therapy
Abstract
Glucokinase (GK) plays a key role in whole-body glucose homeostasis by catalyzing the phosphorylation of glucose in cells that express this enzyme, such as pancreatic β cells and hepatocytes. We describe a class of antidiabetic agents that act as nonessential, mixed-type GK activators (GKAs) that increase the glucose affinity and maximum velocity ( V max ) of GK. GKAs augment both hepatic glucose metabolism and glucose-induced insulin secretion from isolated rodent pancreatic islets, consistent with the expression and function of GK in both cell types. In several rodent models of type 2 diabetes mellitus, GKAs lowered blood glucose levels, improved the results of glucose tolerance tests, and increased hepatic glucose uptake. These findings may lead to the development of new drug therapies for diabetes.
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Cites
The Triumvirate: β-Cell, Muscle, Liver: A Collusion Responsible for NIDDM
DeFronzo, R. A. (1988) · Diabetes · doi:10.2337/diab.37.6.667 · Cited by 2,456
Cited by
Management of type 2 diabetes: new and future developments in treatment
Tahrani, A. A., Bailey, C. J., Del Prato, S., & Barnett, A. H. (2011) · The Lancet · doi:10.1016/s0140-6736(11)60207-9 · Cited by 533
Role of the liver in the control of carbohydrate and lipid homeostasis
Postic, C., Dentin, R., & Girard, J. (2004) · Diabetes & Metabolism · doi:10.1016/s1262-3636(07)70133-7 · Cited by 448
Beer, N. L., Tribble, N. D., McCulloch, L. J., Roos, C., Johnson, P. R. V., Orho-Melander, M., & Gloyn, A. L. (2009) · Human Molecular Genetics · doi:10.1093/hmg/ddp357 · Cited by 401
Molecular Physiology of Mammalian Glucokinase
Iynedjian, P. B. (2009) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-008-8322-9 · Cited by 365
Epigallocatechin Gallate Supplementation Alleviates Diabetes in Rodents
Wolfram, S., Raederstorff, D., Preller, M., Wang, Y., Teixeira, S. R., Riegger, C., & Weber, P. (2006) · The Journal of Nutrition · doi:10.1093/jn/136.10.2512 · Cited by 331
Metadata
- Authors
- Grimsby, J., Sarabu, R., Corbett, W. L., Haynes, N.-E., Bizzarro, F. T., Coffey, J. W., Guertin, K. R., Hilliard, D. W., Kester, R. F., Mahaney, P. E., Marcus, L., Qi, L., Spence, C. L., Tengi, J., Magnuson, M. A., Chu, C. A., Dvorozniak, M. T., Matschinsky, F. M., & Grippo, J. F.
- Venue
- Science
- Published
- 2003-07-18
- Volume
- 301
- Issue
- 5631
- Pages
- 370-373
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2164306929
- Cited by
- 526
- References
- 1
- FWCI
- 30.40
- Type
- journal article
- Language
- en
- Open access
- closed
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- The paper
- Grimsby, J., Sarabu, R., Corbett, W. L., Haynes, N.-E., Bizzarro, F. T., Coffey, J. W., Guertin, K. R., Hilliard, D. W., Kester, R. F., Mahaney, P. E., Marcus, L., Qi, L., Spence, C. L., Tengi, J., Magnuson, M. A., Chu, C. A., Dvorozniak, M. T., Matschinsky, F. M., & Grippo, J. F. (2003). Allosteric Activators of Glucokinase: Potential Role in Diabetes Therapy. Science. https://doi.org/10.1126/science.1084073
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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