Molecular physiology of mammalian glucokinase.
Molecular physiology of mammalian glucokinase.
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DOI：
10.1007/s00018-008-8322-9
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发表时间：
2009-01
影响因子：
8
通讯作者：
Iynedjian, P. B.
中科院分区：
文献类型：
--
作者：
Iynedjian, P. B.
葡萄糖激酶（GCK）基因是最早被确定为人类“糖尿病基因”的候选基因之一。随后，在理解GCK在葡萄糖代谢调节中的影响方面取得了重要进展。通过晶体学的结构解析提供了对GCK的动力学性质的深入了解。发现了GCK的蛋白质相互作用伴侣。基因表达研究揭示了GCK组织分布的新方面，包括在大脑中，以及肝脏中胰岛素对其的调节。结合基因过表达和基因敲除实验的代谢控制分析强调了GCK作为葡萄糖代谢调节剂的独特影响。对人类GCK突变体进行生物化学研究以了解疾病机制。药物开发计划将GCK的小分子激活剂确定为潜在的抗糖尿病药物。这些进展在这里进行了总结，目的是提供一个完整的观点GCK的作用，在分子生理学和医学的葡萄糖稳态。
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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