P9: REGULATION OF VSMC FUNCTION BY THE INSULIN SIGNALING PATHWAY

P9：胰岛素信号通路对 VSMC 功能的调节

• 批准号: 8168191
• 负责人: Thomas Cooper Woods
• 金额: $ 26.56万
• 依托单位: LSU HEALTH SCIENCES CENTER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8168191
• 关键词: Adaptor Signaling Protein; Binding; Blood Vessels; Cell physiology; Computer Retrieval of Information on Scientific Projects Database; Diabetes Mellitus; Drug usage; Funding; Grant; Institution; Insulin; Insulin Receptor; Insulin Resistance; Insulin Signaling Pathway; Link; Measures; Pathway interactions; Phosphotransferases; Protein-Serine-Threonine Kinases; Regulation; Relative (related person); Research; Research Personnel; Resources; Role; Signal Transduction; Sirolimus; Smooth Muscle Myocytes; Source; Stents; Testing; United States National Institutes of Health; cardiovascular disorder risk; diabetic; mTOR protein; prevent; response; response to injury; restenosis

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Diabetes Mellitus increases the risk of cardiovascular disease and the reasons for this remain unclear. Use of drug eluting stents delivering rapamycin to inhibit the mammalian Target of Rapamycin (mTOR) and prevent in-stent restenosis has suggested an altered role for mTOR under diabetic conditions. This project will elucidate the role of insulin and insulin resistance in altering the effects of mTOR inhibition on the vascular response to injury. Insulin binds to the insulin receptor activating both the serine threonine kinase, Akt, and Extra-cellular Signal Regulated Kinases 1 and 2 (ERK1/2). Our hypothesis is: under insulin resistant conditions, stimulation of vascular smooth muscle cells (VSMCs) by insulin leads to increased activation of ERK and a decreased activation of Akt relative to normal VSMCs, diminishing the role the mTOR pathway in the vascular response to injury. We will test this hypothesis in three aims, targeting different levels of the mTOR pathway. Aim 1 will determine whether insulin resistance diminishes the activation of mTOR in response to mitogenic stimulation and measure its effects on downstream components of this pathway. Aim 2 will determine the activation of the ERK1/2 and Akt pathways under insulin resistant conditions. Aim 3 will examine the role of the insulin receptor, its adaptor proteins, and pathways linking Akt and ERK1/2 activity to determine the mechanism generating the effects seen in Aim 2. These aims start at mTOR activation and move outward to determine how diabetes alters its role in the vascular response to injury.

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