Watson Robert T, Pessin Jeffrey E
Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY 11794, USA.
Cell Signal. 2007 Nov;19(11):2209-17. doi: 10.1016/j.cellsig.2007.06.003. Epub 2007 Jun 21.
Insulin regulates circulating glucose levels by suppressing hepatic glucose production and increasing glucose transport into muscle and adipose tissues. Defects in these processes are associated with elevated vascular glucose levels and can lead to increased risk for the development of Type 2 diabetes mellitus and its associated disease complications. At the cellular level, insulin stimulates glucose uptake by inducing the translocation of the glucose transporter 4 (GLUT4) from intracellular storage sites to the plasma membrane, where the transporter facilitates the diffusion of glucose into striated muscle and adipocytes. Although the immediate downstream molecules that function proximal to the activated insulin receptor have been relatively well-characterized, it remains unknown how the distal insulin-signaling cascade interfaces with and recruits GLUT4 to the cell surface. New biochemical assays and imaging techniques, however, have focused attention on the plasma membrane as a potential target of insulin action leading to GLUT4 translocation. Indeed, it now appears that insulin specifically regulates the docking and/or fusion of GLUT4-vesicles with the plasma membrane. Future work will focus on identifying the key insulin targets that regulate the GLUT4 docking/fusion processes.
胰岛素通过抑制肝脏葡萄糖生成并增加葡萄糖向肌肉和脂肪组织的转运来调节循环血糖水平。这些过程中的缺陷与血管内葡萄糖水平升高相关，并可能导致2型糖尿病及其相关疾病并发症的发生风险增加。在细胞水平上，胰岛素通过诱导葡萄糖转运蛋白4（GLUT4）从细胞内储存位点转运至质膜来刺激葡萄糖摄取，在质膜上该转运蛋白促进葡萄糖扩散进入横纹肌和脂肪细胞。尽管紧邻活化胰岛素受体发挥作用的直接下游分子已得到相对充分的表征，但远端胰岛素信号级联如何与GLUT4相互作用并将其招募至细胞表面仍不清楚。然而，新的生化分析和成像技术已将注意力集中在质膜上，将其作为胰岛素作用导致GLUT4转运的潜在靶点。事实上，现在看来胰岛素特异性地调节GLUT4囊泡与质膜的对接和/或融合。未来的工作将集中于确定调节GLUT4对接/融合过程的关键胰岛素靶点。
