Proteomics: Inactivity-induced muscle insulin resistance

描述(申请人提供)：胰岛素抵抗和2型糖尿病 在成人中流行，现在甚至在青少年中发生。减少了…… 体力活动在糖尿病发病率的增加中发挥了重要作用，因为 在许多流行病学和生理学论文中都有记载。伟大的 重要的是，最近的出版物表明，增加的收缩 活动通过胰岛素非依赖性信号增强葡萄糖摄取 信号通路，可能是AMP激酶，但完整的通路仍有待于 勾勒出来的。这些观察的重要性在于，它们提高了 意想不到的新蛋白质将身体不活跃与 会出现胰岛素抵抗。随着后基因组时代的开始， 人类基因组测序，现在有工具可以发现 目前与胰岛素信号无关的蛋白质的特性 通过胰岛素修饰以外的机制产生的抵抗。这项提案将重点放在 关于正常自愿跑步时差异表达的蛋白质 由于将滚轮从保持架上移走而停止，或在高脂肪时停止 饮食被消耗掉了。这些模型模拟了当前久坐不动的生活方式。 和/或高脂肪摄入量。特指I将使用双向凝胶电泳法 骨骼肌差异表达蛋白质的实验测定 体力活动减少的人。《特定目标2》也将 利用双向凝胶电泳法确定差异表达蛋白质 在体力活动减少的大鼠的骨骼肌中 同时吃高脂肪饮食。一种假设是，无论是不活动还是高水平运动 血脂会导致独特的，但不完全相同的一系列与 胰岛素抵抗在骨骼肌中表达。这些蛋白质中的许多 到目前为止，是否会被确认为在骨骼肌胰岛素中发挥作用？ 抵抗。鉴定与胰岛素相关的表达蛋白 骨骼肌中的抵抗力将允许开发新的假说， 它的功能和与其他蛋白质的相互作用将是重点 未来的拨款申请。这样的新假说可能会导致新的治疗方法 治疗糖尿病。这项提案的结果将更好地建立 活跃的骨骼肌与其他器官系统相互作用，以防止 2型糖尿病、动脉粥样硬化和肥胖症的代谢紊乱。

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.