Journal
CELLULAR AND MOLECULAR LIFE SCIENCES
Volume 66, Issue 1, Pages 27-42Publisher
BIRKHAUSER VERLAG AG
DOI: 10.1007/s00018-008-8322-9
Keywords
Glucokinase; diabetes; glucose metabolism; insulin; hexokinase; islet of Langerhans; hepatocyte; MODY
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Funding
- Swiss National Science Foundation
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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.
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