SIGNAL TRANSDUCT OF INSULINS METABOLIC EFFECT

胰岛素代谢作用的信号转导

• 批准号: 2136508
• 负责人: AARON J MORRIS
• 金额: $ 2.37万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-04-10 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2136508
• 关键词: SIGNAL; TRANSDUCT; INSULINS; METABOLIC; EFFECT

Insulin stimulates increased glucose transport into adipose and muscle tissue by causing translocation of the insulin responsive glucose transporter (GLUT4) from an intracellular pool to the plasma membrane. The inability of insulin's target tissues to respond in this manner is one of the primary defects in noninsulin-dependent diabetes mellitus. However, the signaling events that lead to GLUT4 translocation are poorly understood. The focus of this proposal is to investigate the intracellular insulin signaling pathways that trigger GLUT4 translocation. Elucidation of the mechanism whereby insulin stimulates glucose transport may identify new potential targets for therapeutic intervention in insulin resistant states. The experiments will be performed in 3T3-L1 adipocytes, in which insulin-stimulated GLUT4 translocation can be assessed on a single cell basis by immunofluorescence staining with anti GLUT4 antibodies. Microinjection of single living cells will be used to deliver various reagents to activate or inactivate specific intracellular molecules that may be involved in insulin action. Nearly any type of reagent can be delivered in this way, such as antibodies, peptides and recombinant proteins. There are many potentially involved signaling molecules that will be studied with this system, including substrates of the insulin receptor, p21 ras, the Raf, MEK and ERK Ser/Thr kinases, phosphatidylinositol 3-kinase and Rab small GTP-binding proteins.

胰岛素刺激增加葡萄糖向脂肪和肌肉的转运 通过引起胰岛素反应性葡萄糖的易位来组织 转运蛋白（GLUT4）从细胞内池到质膜。 胰岛素的靶组织无法以这种方式做出反应是 非胰岛素依赖型糖尿病的主要缺陷之一。 然而，导致 GLUT4 易位的信号事件却很差。 明白了。该提案的重点是调查 触发 GLUT4 的细胞内胰岛素信号通路 易位。阐明胰岛素刺激的机制 葡萄糖转运可能会确定新的潜在治疗靶点 干预胰岛素抵抗状态。实验将是 在 3T3-L1 脂肪细胞中进行，其中胰岛素刺激 GLUT4 易位可以通过以下方式在单细胞基础上进行评估 使用抗 GLUT4 抗体进行免疫荧光染色。显微注射 的单个活细胞将用于将各种试剂输送到 激活或灭活特定的细胞内分子，这些分子可能是 参与胰岛素作用。几乎可以输送任何类型的试剂 通过这种方式，例如抗体、肽和重组蛋白。那里 有许多可能涉及的信号分子将被研究 有了这个系统，包括胰岛素受体的底物，p21 ras， Raf、MEK 和 ERK Ser/Thr 激酶、磷脂酰肌醇 3-激酶和 Rab 小 GTP 结合蛋白。