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Nat Rev Drug Discov. 2009 May;8(5):399-416. doi: 10.1038/nrd2850. Epub 2009 Apr 17.

Assessing the potential of glucokinase activators in diabetes therapy.

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  • 1University of Pennsylvania, School of Medicine, Department of Biochemistry and Biophysics, 612 Clinical Research Building, Philadelphia, Pennsylvania 19104, USA.


Glucokinase, a unique isoform of the hexokinase enzymes, which are known to phosphorylate D-glucose and other hexoses, was identified during the past three to four decades as a new, promising drug target for type 2 diabetes. Glucokinase serves as a glucose sensor of the insulin-producing pancreatic islet beta-cells, controls the conversion of glucose to glycogen in the liver and regulates hepatic glucose production. Guided by this fundamental knowledge, several glucokinase activators are now being developed, and have so far been shown to lower blood glucose in several animal models of type 2 diabetes and in initial trials in humans with the disease. Here, the scientific basis and current status of this new approach to diabetes therapy are discussed.

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