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Molecular physiology of mammalian glucokinase

Published in Cellular and Molecular Life Sciences. 2009, vol. 66, no. 1, p. 27-42
Collection Open Access - Licence nationale Springer
Abstract The glucokinase (GCK) gene was one of the first candidate genes to be identified as a human "diabetes gene". Subsequently, important advances were made in understanding the impact of GCK in the regulation of glucose metabolism. Structure elucidation by crystallography provided insight into the kinetic properties of GCK. Protein interaction partners of GCK were discovered. Gene expression studies revealed new facets of the tissue distribution of GCK, including in the brain, and its regulation by insulin in the liver. Metabolic control analysis coupled to gene overexpression and knockout experiments highlighted the unique impact of GCK as a regulator of glucose metabolism. Human GCK mutants were studied biochemically to understand disease mechanisms. Drug development programs identified small molecule activators of GCK as potential antidiabetics. These advances are summarized here, with the aim of offering an integrated view of the role of GCK in the molecular physiology and medicine of glucose homeostasis.
Keywords Adaptor Proteins, Signal Transducing/metabolismBrain/enzymologyDiabetes Mellitus, Type 2/drug therapy/enzymology/geneticsGene Expression RegulationGlucose/*metabolismHexokinase/chemistry/genetics/*physiologyHomeostasis/genetics/physiologyHumansInsulin/physiologyIslets of Langerhans/enzymologyLiver/enzymologyMitochondrial Membranes/enzymologyPersistent Hyperinsulinemia Hypoglycemia of Infancy/enzymology/genetics
PMID: 18726182
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IYNEDJIAN, Patrick. Molecular physiology of mammalian glucokinase. In: Cellular and Molecular Life Sciences, 2009, vol. 66, n° 1, p. 27-42. doi: 10.1007/s00018-008-8322-9 https://archive-ouverte.unige.ch/unige:19872

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Deposited on : 2012-04-23

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