Regulation of Glucose Uptake by AS160 in Skeletal Muscle

AS160 对骨骼肌葡萄糖摄取的调节

• 批准号: 7111210
• 负责人: Eric B Taylor
• 金额: $ 4.6万
• 依托单位: JOSLIN DIABETES CENTER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7111210
• 关键词: biological signal transduction; electroporation; glucose metabolism; glucose transport; guanosinetriphosphatase activating protein; hormone regulation /control mechanism; immunoprecipitation; insulin; insulin sensitivity /resistance; laboratory mouse; liquid chromatography mass spectrometry; muscle contraction; noninsulin dependent diabetes mellitus; phosphorylation; postdoctoral investigator; protein localization; protein protein interaction; protein structure function; striated muscles

DESCRIPTION (provided by applicant): A major pathological feature of type 2 diabetes is skeletal muscle insulin resistance. Contraction of skeletal muscle results in a very large increase in glucose uptake independent of insulin. The complete signal transduction pathways mediating contraction and insulin stimulated glucose uptake in skeletal muscle are not known, nor is it understood if or where these signaling pathways converge. Novel research from the Goodyear laboratory has recently provided evidence that the Akt Substrate of 160 kDa (AS160) regulates both contraction and insulin stimulated glucose transport in skeletal muscle. Therefore, the primary objective of my research project is to determine how AS160 regulates glucose transport in skeletal muscle. Determining how AS160 regulates glucose uptake requires elucidation of the temporal-spatial dynamics of the AS160 protein network in response to both contraction and insulin. This will be accomplished by determining the subcellular localization of AS160, identifying sites on the AS160 molecule that are phosphorylated, and disovering novel AS160 interacting proteins. These studies will provide important mechanistic data that could eventually lead to novel therapies for the treatment of type 2 diabetes.

描述(申请人提供)：2型糖尿病的一个主要病理特征是骨骼肌胰岛素抵抗。骨骼肌的收缩导致葡萄糖摄取量的极大增加，而不依赖于胰岛素。介导骨骼肌收缩和胰岛素刺激的葡萄糖摄取的完整信号转导通路尚不清楚，也不清楚这些信号转导通路是否或在哪里汇聚。固特异实验室的新研究最近提供了证据表明，160 kDa的Akt底物(AS160)调节骨骼肌收缩和胰岛素刺激的葡萄糖运输。因此，我的研究项目的主要目标是确定AS160如何调节骨骼肌中的葡萄糖运输。要确定AS160如何调节葡萄糖摄取，需要阐明AS160蛋白质网络对收缩和胰岛素的反应的时空动态。这将通过确定AS160的亚细胞定位，识别AS160分子上被磷酸化的位置，并发现新的AS160相互作用蛋白来实现。这些研究将提供重要的机制数据，最终可能导致治疗2型糖尿病的新疗法。