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: 6834989
• 负责人: ZHI-JIE CHENG
• 金额: $ 5.35万
• 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/6834989
• 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; 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性同工型。胰岛素刺激导致将GLUT4募集到质膜（PM），从而使葡萄糖通量增加进入细胞。证据表明，GLUT4运输的不规则性是肥胖和2型糖尿病的基础。在两种疾病的动物模型中，鞘脂脂（SL）水平升高是典型的。 SLS是一类重要的脂质分子，它们在各种细胞功能中起着作用，包括细胞 - 细胞相互作用，细胞生长，分化以及信号转导。它们与胆固醇相互作用以形成膜模量。该提议中检验的一般假设是GLUT4运输受SL和胆固醇的调节。如特定目的所示，我们将研究SLS和胆固醇在胰岛素反应性GLUT4易位和内在化中的作用。拟议的研究的结果将促进我们在疾病状态下的GLUT4运输和功能的理解，并提供潜在的治疗方法。