Regulation of Glucose Transporter Trafficking by Lipids

脂质对葡萄糖转运蛋白运输的调节

• 批准号: 7026385
• 负责人: ZHI-JIE CHENG
• 金额: $ 5.59万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-03-01 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7026385
• 关键词: 3T3 cells; SDS polyacrylamide gel electrophoresis; biological signal transduction; biological transport; cell membrane; cholesterol; confocal scanning microscopy; endocytosis; exocytosis; fluorescent dye /probe; glucose transporter; green fluorescent proteins; immunoprecipitation; insulin; insulin receptor; molecular dynamics; phosphorylation; postdoctoral investigator; receptor expression; sphingolipids

DESCRIPTION (provided by applicant): Among the glucose transporter (GLUT) family, GLUT4 is unique in that it is confined mainly to insulin-sensitive fat and muscle tissues and is the major insulin-responsive isoform. Insulin stimulation results in the recruitment of GLUT4 to the plasma membrane (PM), thereby allows increased glucose flux into the cells. Evidences indicate that irregularities in GLUT4 trafficking underlie obesity and type 2 diabetes. Elevated levels of sphingolipids (SLs) such as ceramide and ganglioside GM3 are typical in animal models of both diseases. SLs are an important class of lipid molecules that play roles in a wide variety of cell functions including cell-cell interaction, cell growth and differentiation and signal transduction. They interact with cholesterol to form membrane micordomains. The general hypothesis tested in this proposal is that GLUT4 trafficking is regulated by SL and cholesterol. As indicated in the Specific Aims, we will investigate the role of SLs and cholesterol in insulin-responsive GLUT4 translocation and internalization. The results from the proposed study will facilitate our understanding the GLUT4 trafficking and function in disease state and provide potential therapeutic approaches.

描述（由申请人提供）：在葡萄糖转运蛋白（GLUT）家族中，GLUT4的独特之处在于它主要局限于胰岛素敏感的脂肪和肌肉组织，并且是主要的胰岛素反应亚型。胰岛素刺激导致 GLUT4 募集到质膜 (PM)，从而增加进入细胞的葡萄糖流量。有证据表明，GLUT4 运输的不规则性是肥胖和 2 型糖尿病的基础。在这两种疾病的动物模型中，神经酰胺和神经节苷脂 GM3 等鞘脂 (SL) 水平升高是典型的。 SL 是一类重要的脂质分子，在多种细胞功能中发挥作用，包括细胞间相互作用、细胞生长和分化以及信号转导。它们与胆固醇相互作用形成膜微结构域。该提案测试的一般假设是 GLUT4 运输受 SL 和胆固醇调节。如具体目标所示，我们将研究 SL 和胆固醇在胰岛素响应 GLUT4 易位和内化中的作用。拟议研究的结果将有助于我们了解疾病状态下的 GLUT4 运输和功能，并提供潜在的治疗方法。