Molecular physiology of mammalian glucokinase

Article Article scientifique Article Molecular physiology of mammalian glucokinase eng 2009 author Iynedjian Patrick 22047 27-42 10.1007/s00018-008-8322-9 18726182 1420-682X 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. Adaptor Proteins, Signal Transducing/metabolism Brain/enzymology Diabetes Mellitus, Type 2/drug therapy/enzymology/genetics Gene Expression Regulation Glucose/*metabolism Hexokinase/chemistry/genetics/*physiology Homeostasis/genetics/physiology Humans Insulin/physiology Islets of Langerhans/enzymology Liver/enzymology Mitochondrial Membranes/enzymology Persistent Hyperinsulinemia Hypoglycemia of Infancy/enzymology/genetics Dewey 610 Open Access - Licence nationale Springer 3 Faculté de médecine 2 false Cellular and molecular life sciences 66 1 e5aad950-765f-4e3a-bd63-c090f6369972 Article (Published version) Public file1.pdf 522953 application/pdf openAccess Faculté de médecine

Title	Published in	Access level	OA Policy	Year	Views	Downloads

Molecular physiology of mammalian glucokinase	Cellular and molecular life sciences			2009	645	373

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Iynedjian, Patrick