DEFINING THE MOLECULAR COMPONENTS OF GLUT4 TRANSLOCATION

在脂肪组织和骨骼肌中，胰岛素诱导易位 将含有GLUT 4的囊泡释放到细胞表面，导致细胞内的细胞凋亡。 葡萄糖摄取增加。 GLUT 4易位的机制 是很难理解的。 最近，几种蛋白质参与了调节 神经和神经内分泌组织中的胞吐作用已被证明 在胰岛素敏感组织中表达。 这些蛋白质 SNARE复合体的组成部分。 此外， RAB家族的小GTP结合蛋白，参与 受调节的内吞作用/胞吐作用也存在于脂肪细胞中， 骨骼肌。 虽然这些蛋白质与 胰岛素调节GLUT 4易位没有功能作用， 测定 然而，我们最近发现，陷阱- Rab家族的复杂蛋白和特定成员是 GLUT 4易位机制中的必要成分。我们 还发现了一种潜在的新蛋白质， 胰岛素调节脂肪细胞中的Rabs。 才是目的 这项建议扩大了我们的初步意见，包括 更详细的生化和细胞生物学分析， 分子。 这些研究将包括旨在 研究蛋白质间相互作用的特异性， SNARE蛋白及其受胰岛素调节， 其他新的Rab-interacting蛋白和追求他们的分子 克隆。 这些研究的数据将使我们能够定义一个更 胰岛素调节葡萄糖摄取的当代模型。

In adipose tissue and skeletal muscle insulin induces the translocation o f GLUT4-containing vesicles to the ell surface resulting in an increase in glucose uptake. The mechanism of GLUT4 translocation is poorly understood. Recently several proteins involved in regulated exocytosis in neural and neuroendocrine tissues have been shown to be expressed in insulin-sensitive tissues. These proteins are components of the SNARE complex. In addition, members of the RAB family of small GTP-binding proteins that are involved in regulated endocytosis/exocytosis are also present in adipocytes and skeletal muscle. While these proteins have been implicated in insulin-regulated GLUT4 translocation no functional role has been determined. However, we have recently established that SNARE- complex proteins and specific members of the Rab family are necessary components in the GLUT4 translocation machinery. We have also identified a potentially novel protein that interacts with Rabs in adipocytes in an insulin-regulated manner. It is the purpose of this proposal to extend our preliminary observations to include a more detailed biochemical and cell biological analysis of these molecules. These studies will include experiments designed to investigate the specificity of protein-protein interactions between the SNARE proteins and their regulation by insulin, identification of other novel Rab-interacting proteins and pursuit of their molecular cloning. Data from these studies will allow us to define a more contemporary model of insulin-regulated glucose uptake.