Function and pathophysiological role of a novel glucose transporter expressed in skeletal muscle

糖尿病是一种代谢紊乱，由胰岛素缺乏和存在的胰岛素作用缺陷共同引起。最突出的代谢异常是高血糖，胰岛素治疗往往不能令人满意地纠正这一点。高血糖的主要原因之一是肌肉组织对葡萄糖的摄取减少。胰岛素促进葡萄糖进入肌肉细胞的机制涉及动员葡萄糖转运蛋白家族中的一种特定蛋白，该蛋白已被命名为GLUT4。令人惊讶的是，经过基因改造以消除或敲除GLUT4产生的动物不会患上糖尿病。这一发现导致了一种理论，即当GLUT4功能出现问题时，存在一种备用葡萄糖转运蛋白，可以预防糖尿病。我们最近发现了葡萄糖转运蛋白家族的一个新成员，它可能作为GLUT4的平行或备份系统发挥作用。这种新的葡萄糖转运蛋白，我们称之为GLUT8，存在于人类肌肉组织中，在其他细胞中的研究表明，它改变了它在细胞内的分布，以响应胰岛素。我们现在想更详细地研究这种新的葡萄糖转运蛋白在肌肉组织中的作用，以及它与GLUT4相比是如何发挥作用的。特别是，我们认为，当GLUT4的动员存在问题，而且GLUT8的生产或功能存在缺陷时，2型糖尿病可能会发生。如果是这样的话，增加GLUT8的产量可能会改善葡萄糖向肌肉组织的运输，从而改善糖尿病患者的血糖水平控制。

Diabetes is a disorder of metabolism resulting from a combination of deficiency of insulin and defective action of the insulin that is present. The most prominent metabolic abnormality is high blood glucose, which is often not satisfactorily corrected by insulin treatment. One of the main reasons for the high blood glucose is reduced uptake of glucose by muscle tissue. The mechanism by which insulin enhances glucose entry into muscle cells involves mobilisation of a specific protein from the glucose transporter protein family, which has been designated GLUT4. Surprisingly, animals that have been genetically altered to eliminate orknockout GLUT4 production do not develop diabetes. This finding has led to the theory that there is a backup glucose transporter protein that can prevent diabetes when there is a problem with GLUT4 function. We have recently discovered a new member of the glucose transporter protein family that could potentially function as either a parallel or a backup system for GLUT4. This new glucose transporter, which we have called GLUT8, is present in human muscle tissue and studies in other cells have shown that it alters its distribution within the cell in reponse to insulin. We now want to study in more detail the role of this new glucose transporter in muscle tissue and how it functions compared with GLUT4. In particular, we think it is possible that Type 2 diabetes occurs when there is not only a problem with the mobilisation of GLUT4 but also a defect in the production or function of GLUT8. If this is the case, then increasing GLUT8 production might improve glucose transport into muscle tissue and so improve control of blood glucose levels in diabetes.