Role of JNK1 in Skeletal Muscle Glucose Metabolism

JNK1 在骨骼肌葡萄糖代谢中的作用

• 批准号: 7167152
• 负责人: Carol Ann Witczak
• 金额: $ 4.73万
• 依托单位: JOSLIN DIABETES CENTER
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-12-01 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7167152
• 关键词: JUN kinase; biological signal transduction; exercise; genetically modified animals; glucose metabolism; glycogen; insulin; intracellular; laboratory mouse; noninsulin dependent diabetes mellitus; postdoctoral investigator; striated muscles

DESCRIPTION (provided by applicant): Physical exercise exerts a salutary effect on the onset, progression, and severity of type 2 diabetes. However, little is known regarding the mechanisms underlying the beneficial effects of exercise on skeletal muscle. Recent studies have suggested a role for the stress-activated kinase, c-jun-NH2-terminal kinase isoform 1 (JNK1), in the regulation of whole body glucose metabolism. It is currently not known whether the effects of JNK1 signaling are mediated via alterations in glucose metabolism in skeletal muscle. The overall goal of this proposal is to determine the physiological consequences of JNK1 signaling on skeletal muscle responses to insulin and acute bouts of exercise. Specifically, the experiments outlined in this proposal will test the hypothesis that JNK1 deficiency alters the ability of insulin and exercise to regulate skeletal muscle glucose uptake, glycogen synthesis, and intracellular signaling proteins involved in glucose metabolism. Ultimately, these studies will help to define the molecular mechanisms underlying type 2 diabetes and the beneficial effects of physical exercise on skeletal muscle glucose metabolism. Also, these studies may uncover new pharmacological targets for the treatment of type 2 diabetes.

描述（由申请人提供）：体育锻炼对2型糖尿病的发作，进展和严重程度产生有益的影响。但是，关于运动对骨骼肌有益作用的基本机制知之甚少。最近的研究表明，应激激活激酶C-JUN-NH2-末端激酶同工型1（JNK1）在整个体内葡萄糖代谢的调节中起作用。目前尚不清楚JNK1信号的作用是否是通过骨骼肌中葡萄糖代谢的改变来介导的。该提案的总体目标是确定JNK1信号传导对骨骼肌对胰岛素和急性运动急性反应的生理后果。具体而言，该提案中概述的实验将检验以下假设：JNK1缺乏症会改变胰岛素和运动调节骨骼肌葡萄糖摄取，糖原合成以及涉及葡萄糖代谢的细胞内信号传导蛋白的能力。最终，这些研究将有助于定义2型糖尿病基础的分子机制以及体育锻炼对骨骼肌葡萄糖代谢的有益作用。同样，这些研究可能会发现2型糖尿病治疗的新药理靶标。

项目成果

Highly efficient, functional engraftment of skeletal muscle stem cells in dystrophic muscles.

• DOI: 10.1016/j.cell.2008.05.049
• 发表时间: 2008-07-11
• 期刊: Cell
• 影响因子: 64.5
• 作者: Cerletti M;Jurga S;Witczak CA;Hirshman MF;Shadrach JL;Goodyear LJ;Wagers AJ
• 通讯作者: Wagers AJ