Regulation of Serine/Threonine Kinases in Skeletal Muscle

描述（由申请人提供）：运动对2型糖尿病的治疗和预防有有益的影响。体育活动激活骨骼肌中多种代谢信号通路，并随着时间的推移诱导代谢基因表达的改变。一种新的蛋白，蔗糖非发酵蛋白激酶1 / ampk相关激酶（SNARK），已被确定为骨骼肌中一个假定的信号蛋白，并被假设调节多种代谢功能。研究表明，SNARK在骨骼肌中表达，并且发现运动和收缩会增加啮齿动物和人类骨骼肌中SNARK的活性。本项目的总体目标是阐明SNARK在骨骼肌运动调节中的调控和功能。为此，我们确定了四个具体目标：1)阐明骨骼肌中SNARK激活的机制；2)确定SNARK是否介导骨骼肌脂肪酸代谢；3)确定SNARK信号在运动训练诱导的骨骼肌适应中的作用；4)确定骨骼肌SNARK在全身代谢中的功能。阐明SNARK的功能对于理解运动刺激的代谢适应具有重要意义，并有可能为2型糖尿病的治疗和预防确定新的药理学靶点。公共卫生相关性：糖尿病是一个主要的公共卫生问题，运动在治疗和预防这种疾病方面具有无可争议的作用。本研究计划的目的是确定新型ampk相关激酶SNARK在调节骨骼肌运动代谢反应中的作用。这将有助于更好地了解运动对糖尿病的有益影响，并有助于确定糖尿病的新疗法。

DESCRIPTION (provided by applicant): Exercise has beneficial effects on the treatment as well as prevention of type 2 diabetes. Physical activity activates diverse metabolic signaling pathways in skeletal muscle, and over time induces modification of metabolic gene expression. A novel protein, sucrose-non-fermenting protein kinase 1 /AMPK-related kinase (SNARK), has been identified as a putative signaling protein in skeletal muscle and has been hypothesized to regulate multiple metabolic functions. Studies have shown that SNARK is expressed in skeletal muscle and it was found that exercise and contraction increase SNARK activity in both rodent and human skeletal muscle. The overall goal of the proposed research project is to elucidate the regulation and function of SNARK in mediating the effects of exercise in skeletal muscle. For this purpose, four specific aims were identified: 1) To elucidate the mechanism of SNARK activation in skeletal muscle; 2) To determine whether SNARK mediates fatty acid metabolism in skeletal muscle; 3) To determine the role of SNARK signaling in exercise training- induced adaptations in skeletal muscle; and 4) To determine the function of skeletal muscle SNARK in whole body metabolism. Elucidating the function of SNARK will be important in understanding exercise-stimulated metabolic adaptations and has the potential to define new pharmacological targets for both treatment and prevention of type 2 diabetes. PUBLIC HEALTH RELEVANCE: Diabetes is a major public health concern and exercise has an undisputed role in the treatment and prevention of this disease. The goal of this research proposal is to determine the role of the novel AMPK-related kinase SNARK in regulating metabolic responses to exercise in skeletal muscle. This will lead to a better understanding of the beneficial effects of exercise in diabetes and could help to identify novel therapies for diabetes.