Proteomics: Inactivity-induced muscle insulin resistance

蛋白质组学：不活动引起的肌肉胰岛素抵抗

• 批准号: 6440042
• 负责人: FRANK W BOOTH
• 金额: $ 7.25万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-28 至 2003-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6440042
• 关键词: SDS polyacrylamide gel electrophoresis; biological signal transduction; blood lipid; dietary lipid; glucose tolerance; glucose transporter; insulin sensitivity /resistance; laboratory rat; matrix assisted laser desorption ionization; muscle proteins; proteomics; restricted physical activity; striated muscles

DESCRIPTION (provided by applicant): Insulin resistance and type 2 diabetes are epidemic in adults, and are now even occurring in adolescents. A decrease in physical activity has played an important role in this increase in diabetes as documented in many epidemiological and physiological papers. Of great significance are recent publications showing that increased contractile activity signals an enhanced glucose uptake through an insulin-independent signaling pathway, likely AMP kinase, but the complete pathway remains to be delineated. The importance of these observations is that they raise the probability that unexpected novel proteins linking physical inactivity to insulin resistance will be found. As the post-genome era begins with the sequencing of the human genome, tools are now available to discover the identity of proteins currently unassociated with the signaling of insulin resistance by mechanisms other than insulin modification. This proposal focuses on those proteins differentially expressed when either normal voluntary running ceases due to the removal of a running wheel from the cage, or when high fat diets are consumed. These models mimic current lifestyles of sedentary activity and/or high fat consumption. Specific aim I will use 2-D gel electrophoresis to experimentally determine differentially expressed proteins in skeletal muscle that have undergone decreased physical activity. Specific aim 2 will also employ 2-D gel electrophoresis to determine differentially expressed proteins in the skeletal muscle of rats that have undergone decreased physical activity while eating a high fat diet. One hypothesis is that both inactivity and high blood lipids will cause unique, but not identical, sets of proteins related to insulin resistance to be expressed in skeletal muscle. Many of these proteins will heretofore be unidentified as playing a role in skeletal muscle insulin resistance. Identifying the expressed proteins associated with insulin resistance in skeletal muscle will permit the development of new hypotheses, whose functions and interactions with other proteins will be the focus of future grant applications. Such new hypotheses could lead to new therapies against diabetes. Outcomes of this proposal will better establish that healthy active skeletal muscles interact with other organ systems to prevent the metabolic disorders of type 2 diabetes, atherosclerosis, and obesity.

描述（由申请人提供）：胰岛素抵抗和2型糖尿病是 在成年人中流行，现在甚至发生在青少年中。减少 体力活动在糖尿病的增加中起了重要作用， 在许多流行病学和生理学论文中都有记载。大 重要的是最近的出版物显示， 活性信号通过胰岛素非依赖性 信号通路，可能是AMP激酶，但完整的通路仍然是 描绘的。这些观察的重要性在于，它们提出了 可能性，意想不到的新蛋白质连接身体不活动， 随着后基因组时代的到来， 随着人类基因组测序的完成，现在有了发现 目前与胰岛素信号传导无关的蛋白质的身份 胰岛素修饰以外的机制引起的耐药。该提案重点 这些蛋白质的差异表达，无论是正常的自愿运行， 由于从笼中取出运行轮而停止，或者当高脂肪 饮食是消耗的。这些模型模拟了当前久坐不动的生活方式 和/或高脂肪消耗。具体目的我将使用二维凝胶电泳， 实验确定骨骼肌中差异表达的蛋白质 他们的身体活动减少了。具体目标2还将 采用二维凝胶电泳确定差异表达蛋白 在体力活动减少的大鼠的骨骼肌中 同时吃高脂肪食物一种假设是，不活动和高血压都是一种疾病。 血脂会导致独特的，但不相同的，与蛋白质相关的蛋白质组， 胰岛素抵抗在骨骼肌中表达。许多这些蛋白质 迄今为止还没有发现在骨骼肌胰岛素中起作用 阻力鉴定与胰岛素相关的表达蛋白 骨骼肌中的阻力将允许新的假设的发展， 其功能和与其他蛋白质的相互作用将是研究的重点。 未来的补助金申请这些新的假设可能会导致新的治疗方法 对抗糖尿病这项建议的结果将更好地建立健康的 活跃的骨骼肌与其他器官系统相互作用， 2型糖尿病、动脉粥样硬化和肥胖症的代谢紊乱。