Analysis of the Role of Vesicle Docking/Fusion Proteins in Trafficking of the Glut4 Glucose Transporter in Adipocytes

囊泡对接/融合蛋白在脂肪细胞中 Glut4 葡萄糖转运蛋白运输中的作用分析

• 批准号: nhmrc : 143665
• 负责人: Dr Tony Rowe
• 金额: $ 14.14万
• 依托单位: Monash University
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2001
• 资助国家: 澳大利亚
• 起止时间: 2001-01-01 至 2003-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/analysis-role-vesicle-transporter-adipocytes/96973
• 关键词: Analysis; Role; Vesicle; Docking; Fusion

The objective of these studies is to understand the molecular mechanisms that are involved in the control of blood glucose levels by the hormone insulin. Elevated blood glucose levels following a meal stimulate the pancreas to release insulin into the circulation. Insulin acts to reduce blood sugar levels by stimulating the uptake of glucose into fat and muscle and suppressing glucose production by the liver. Defects in insulin action in these tissues are the primary cause of Type II diabetes. The debilitating effects of Type II diabetes, the dramatic increase its incidence, and the expense of treating the symptoms of diabetic complications have lead to the realization that the disease represents a major health problem requiring substantial research and development efforts. The project will focus on insulin regulation of glucose uptake in fat cells. Insulin promotes glucose uptake into fat by activating an intracellular signaling pathway that triggers the translocation of a unique glucose transporter protein (Glut4) from storage sites inside the cell to the cell surface. Glut4 translocation is mediated by small membrane vesicles that function to sequester the glucose transporter inside cells in the absence of insulin, and to shuttle Glut4 to the cell surface in response to the hormone. Despite the central importance of this event to the maintenance of normal blood glucose levels, it is poorly understood. The studies will be directed towards investigating the cellular machinery involved in the latter stages of insulin-stimulated glucose uptake- the vesicle-mediated delivery of Glut4 to the cell surface. The objective of these studies is to better understand the molecular basis for Glut4 translocation, and regulation by the insulin signaling cascade. Accomplishment of this goal may suggest potential drug intervention strategies aimed at enhancing insulin-stimulated Glut4 translocation and promoting improved control of blood glucose levels in Type II diabetes.

这些研究的目的是了解胰岛素控制血糖水平的分子机制。餐后血糖水平升高刺激胰腺释放胰岛素进入循环。胰岛素通过刺激脂肪和肌肉对葡萄糖的摄取并抑制肝脏产生葡萄糖来降低血糖水平。这些组织中胰岛素作用的缺陷是II型糖尿病的主要原因。II型糖尿病的衰弱作用、其发病率的急剧增加以及治疗糖尿病并发症症状的费用已经导致认识到该疾病代表了需要大量研究和开发努力的主要健康问题。该项目将集中于胰岛素对脂肪细胞葡萄糖摄取的调节。胰岛素通过激活细胞内信号通路促进葡萄糖摄取到脂肪中，该信号通路触发独特的葡萄糖转运蛋白（Glut 4）从细胞内的储存位点易位到细胞表面。Glut 4易位由小膜囊泡介导，其功能是在不存在胰岛素的情况下将葡萄糖转运蛋白隔离在细胞内，并响应于激素将Glut 4穿梭到细胞表面。尽管该事件对维持正常血糖水平至关重要，但对其了解甚少。这些研究将针对研究胰岛素刺激葡萄糖摄取后期阶段所涉及的细胞机制-囊泡介导的Glut 4向细胞表面的递送。这些研究的目的是更好地了解Glut 4易位的分子基础，以及胰岛素信号级联的调节。这一目标的实现可能表明潜在的药物干预策略，旨在增强胰岛素刺激的Glut 4易位，促进改善II型糖尿病患者血糖水平的控制。