Abstract
Glucokinase (GK) is a molecular sensor that regulates glucose induced insulin secretion in pancreatic β-cells and glucose homeostasis in the liver via catalysis of glucose to glucose-6-phosphate. The recent discovery and development of small molecule glucokinase activators represents a potentially important development for the management of type 2 diabetes. Since the discovery of the first orally active small molecule GK activator RO0281675, a number of research groups have reported the identification of potent activators. In this review, the biological significance of GK in whole body glucose homeostasis is briefly described coupled with the recent progress regarding the identification of novel small molecule GK activators.
Keywords: Glucokinase activator, permanent neonatal diabetes mellitus (PNDM), RO0281675, spirocyclopropane, nicotinamide
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