Regulation of Serine/Threonine Kinases in Skeletal Muscle

骨骼肌中丝氨酸/苏氨酸激酶的调节

• 批准号: 7751648
• 负责人: LAURIE J GOODYEAR
• 金额: $ 39.18万
• 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: 2004-04-01 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7751648
• 关键词: 5' -AMP-activated protein kinase; Ablation; Acute; Area; Binding; Calmodulin; Carrier Proteins; Cell Nucleus; Cell physiology; Chronic; Cytoplasm; Data; Defect; Diabetes Mellitus; Dominant-Negative Mutation; Exercise; Fatty Acids; Fatty acid glycerol esters; Fiber; Gene Expression; Glucose; Goals; Health; Health Benefit; Homeostasis; Human; Insulin Resistance; Knock-out; Knockout Mice; Lead; Mediating; Mediator of activation protein; Metabolic; Metabolism; Mitochondria; Modification; Molecular; Mus; Muscle; Muscle Contraction; Muscle Fibers; Non-Insulin-Dependent Diabetes Mellitus; Phosphorylation; Phosphorylation Site; Phosphotransferases; Physical activity; Play; Prevention; Process; Protein Kinase; Protein-Serine-Threonine Kinases; Proteins; Public Health; Regulation; Research Project Grants; Research Proposals; Rodent; Role; STK11 gene; Signal Pathway; Signal Transduction; Signaling Protein; Skeletal Muscle; Sucrose; Testing; Time; Tissues; Training; Transgenic Mice; Transgenic Organisms; Triglycerides; Work; blood glucose regulation; cell type; diabetes mellitus therapy; disorder prevention; fatty acid metabolism; fatty acid oxidation; feeding; genetic regulatory protein; glucose metabolism; glucose uptake; insulin tolerance; lipid metabolism; novel; public health relevance; response; upstream kinase

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.

描述（由申请人提供）：运动对治疗以及预防2型糖尿病具有有益的影响。体育活动会激活骨骼肌中各种代谢信号通路，并且随着时间的流逝会诱导代谢基因表达的改变。一种新型的蛋白质 - 非蔗糖发酵蛋白激酶1 /与AMPK相关的激酶（SNARK）已被鉴定为骨骼肌中推定的信号传导蛋白，并已被认为可以调节多种代谢功能。研究表明，Snark在骨骼肌中表达，发现运动和收缩会增加啮齿动物和人类骨骼肌的鼻涕活性。拟议的研究项目的总体目标是阐明SNARK在介导骨骼肌效果中的调节和功能。为此，确定了四个特定的目标：1）阐明骨骼肌中的Snark激活机制； 2）确定Snark是否介导骨骼肌中的脂肪酸代谢； 3）确定Snark信号在运动训练中的作用 - 骨骼肌的适应性； 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至关重要，并且有可能定义新的药理学靶标，以治疗和预防2型糖尿病。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中无可争议的作用。该研究建议的目的是确定新型AMPK相关激酶SNARK在调节骨骼肌运动代谢反应中的作用。这将使人们更好地了解运动对糖尿病的有益作用，并有助于鉴定糖尿病的新疗法。