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

这些研究的目的是了解胰岛素控制血糖水平的分子机制。饭后血糖升高会刺激胰腺将胰岛素释放到血液循环中。胰岛素的作用是通过刺激脂肪和肌肉吸收葡萄糖，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型糖尿病的衰弱效应、发病率的急剧增加以及治疗糖尿病并发症症状的费用使人们认识到，这种疾病是一个主要的健康问题，需要进行大量的研究和开发工作。该项目将重点研究胰岛素对脂肪细胞中葡萄糖摄取的调节。胰岛素通过激活细胞内信号通路促进葡萄糖被脂肪吸收，该信号通路触发一种独特的葡萄糖转运蛋白（Glut4）从细胞内的储存位点转运到细胞表面。Glut4易位是由膜小泡介导的，其功能是在缺乏胰岛素的情况下将葡萄糖转运蛋白隔离在细胞内，并在激素的作用下将Glut4运送到细胞表面。尽管这一事件对维持正常血糖水平至关重要，但人们对其了解甚少。这些研究将朝向研究胰岛素刺激的葡萄糖摄取后期的细胞机制——囊泡介导的Glut4向细胞表面的递送。这些研究的目的是更好地了解Glut4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提示潜在的药物干预策略，旨在增强胰岛素刺激的Glut4易位，促进II型糖尿病血糖水平的改善控制。

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.