Identification of insulin specific signal transduction pathways in adipocytes

胰岛素抵抗，代表胰岛素不能调节适当靶组织如肌肉和脂肪组织中的代谢，导致许多疾病，包括糖尿病和肥胖症。这些组织中的关键代谢步骤是从血流中摄取葡萄糖。这一步骤被胰岛素加速，从而允许餐后从血液中有效清除葡萄糖。我们的实验室在显示胰岛素通过刺激葡萄糖转运蛋白从细胞内部移动到细胞表面来调节葡萄糖摄取到肌肉和脂肪组织中方面发挥了重要作用（参见http：--www.imb.uq.edu.au-groups-james-journal 4以获得该过程的动画描述）。在目前的建议中，我们将采取一些策略来剖析连接胰岛素受体和葡萄糖转运蛋白运动的信号转导途径。这些分子的鉴定将为这个重要的谜题提供缺失的部分。一旦解决了这个问题，我们将拥有一套新的目标，用于设计对抗胰岛素抵抗性疾病的药物。

Insulin resistance, which represents an inability of insulin to regulate metabolism in appropriate target tissues such as muscle and adipose tissue, contributes to a number of diseases including diabetes and obesity. A key metabolic step in these tissues is the uptake of glucose from the blood stream. This step is accelerated by insulin thus allowing efficient clearance of glucose from the bloodstream after a meal. Our laboratory has played a major role in showing that insulin regulates glucose uptake into muscle and adipose tissue by stimulating the movement of a glucose transport protein from inside the cell to the cell surface (see http:--www.imb.uq.edu.au-groups-james-glut4 for an animated description of this process). In the present proposal we will pursue a number of strategies to dissect the signal transduction pathways that connect the insulin receptor to the movement of this glucose transporter. Identification of these molecules will provide the missing pieces to this important puzzle. Once solved we will have at our disposal a novel set of targets for designing drugs that will combat insulin resistant diseases.