肌肉因子白介素15在运动改善胰岛素抵抗中的作用及机制

Insulin resistance (IR) refers to tissues have a diminished ability to respond to the action of insulin. Appropriate exercise is the most effective method to improve IR, but the direct material of exercise has not been clarified. Myokine interleukin 15 (IL-15), the cytokine expressed in skeletal muscle most abundantly can improve skeletal muscle IR significantly. In preliminary work, we found treadmill running increased the expression of IL-15 in skeletal muscle in high fat diet induced IR rats. In present project, we observe the change of skeletal muscle endogenous IL-15 expression after exercise training in vivo and in vitro IR models, investigate the alteration of skeletal muscle glucose uptake and the pathway of insulin receptor signal in vivo and in vitro IL-15 knockout model and test whether the effect of exercise on IR is depended by IL-15. In addition, we observed the expression of endoplasmic reticulum stress protein markers, screened the molecular target and explored the mechanism of signal transduction of IL-15 anti endoplasmic reticulum stress. On the basis of the above study, we want to demonstrate that IL-15 is an endogenous protective substance involving in exercise improved IR, to explore the molecular mechanisms of IL-15 and elucidated the mechanism of exercise improved IR.

胰岛素抵抗(insulin resistance, IR)是指胰岛素靶组织对胰岛素的敏感性降低，胰岛素介导的葡萄糖利用率下降的一种状态。合理的运动是IR防治最有效的方法，但其物质基础尚未阐明。肌肉因子白介素15(interleukin-15，IL-15)是骨骼肌中表达最丰富的细胞因子，具有显著的改善骨骼肌IR的效应。本项目在我们前期工作观察到运动促进肥胖IR大鼠骨骼肌IL-15的表达的基础上，拟于在体和离体IL-15敲除或IL-15受体敲除模型上，以骨骼肌葡萄糖摄入、胰岛素受体后信号通路等为指标，观察运动抗IR是否为肌肉因子IL-15依赖；以内质网应激标志蛋白为指标，观察IL-15抗内质网应激作用及其分子靶点；以IL-15受体后信号通路为切入点，观察IL-15抗内质网应激的信号转导机制，以论证肌肉因子IL-15是机体运动改善IR的内源性保护物质，探讨其细胞分子机制，阐明运动改善IR的机制。

胰岛素抵抗(insulin resistance, IR)是指胰岛素靶组织对胰岛素的敏感性降低，胰岛素介导的葡萄糖利用率下降的一种状态。合理的运动是IR防治最有效的方法，但其物质基础尚未阐明。本项目于肥胖诱导的IR大鼠模型上，观察跑台运动对骨骼肌毛细血管密度、骨骼肌纤维类型、骨骼肌脂质沉积的作用，测定IL-15、apelin/APJ、肌联素、irisin和血管内皮生长因子B等肌肉因子的内源性改变。在离体油酸和棕榈酸酯诱导的C2C12肌管细胞IR模型上，观察电脉冲刺激诱导肌细胞收缩对脂质沉积和代谢的作用，测定内源性肌肉因子的改变，以论证肌肉因子在机体运动改善IR的内源性保护作用，阐明运动改善IR的机制。