运动干预对II型糖尿病的预防与治疗：运动诱导的Irisin 对miR-143介导的细胞自噬功能状态在II型糖尿病中的调控作用与机制

Diabetes as one of the high incidence diseases could result in the significant impact on the health and life of large amount of people. It is well known that regular exercise is benefit to the prevention and treatment of diabetes; however, its underlying mechanisms are still unclear. Based on the characteristics of low irisin expression, deficient or dysfunctional autophagy and accelerated apoptosis in diabetes, we would like to use STZ-induced rats with diabetes as the experimental subjects. Following regular swimming training, blood glucose, irisin, miR-143 and related biochemical indicators associated with diabetes in STZ-induced diabetic rats will be quantitatively determined; the damage of pancrea tissue will be evalauted by HE staining or IHC analysis, and the damage of mitochondria and the number of autophagosomes will be analyzed by transmission electron microscope; the proteins and genes associated with autophagy, apoptosis, energy metabolism, insulin resistance, or mitochondrial quality control will be subjected to Western blot, or real-time polymerase chain reaction (RT-PCR), which will be benefit for exploring the correlation between diabetes and autophagy functional status, and confirming our hypothesis that exercise-induced irisin or microRNA-143-mediated autophagy can control blood glucose, reduce insulin resistance, mitigate the damage of islet β cells, as well as identifying the signal pathway network or targets for the prevention, control and treatments of diabetes during exercise intervention. In the present study, we will first propose the role of irisin- or miR-143-mediated autophagy in controlling blood glucose, improving insulin sensitivity, maintaining homeostasis, enhancing mitochondrial quality, preventing and treating diabetes, which will provide a theoretical basis for prevention and treatment of diabetes mellitus. In addition, on the basis of exploring its signal pathways and targets, it can provide the new theoretical basis and ideas for novel and effective intervention strategies or drug development for the targeted therapy of diabetes.

糖尿病严重影响着人们健康与生活, 运动有益于其预防、控制与治疗, 但作用机制还不明确。本研究基于糖尿病具有Irisin水平低下、细胞自噬功能缺陷等特点, 以STZ诱导的糖尿病大鼠为研究对象，对运动干预后糖尿病大鼠血糖、Irisin、miR-143等指标的测定；胰腺组织内线粒体与自噬溶酶体的电镜观察；自噬、胰岛素抵抗、线粒体质量控制相关蛋白或基因的Western bot 与RT-PCR分析，以致力于确立糖尿病与自噬信号通路调控的相关性，探讨Irisin或miR-143介导的自噬调控在糖尿病防治中的作用，探明其调控的信号通路或靶点。本研究首次提出了运动诱导Irisin与 miR-143介导的自噬在控制血糖水平、维持内环境稳定、预防与治疗糖尿病中的作用, 为糖尿病预防与治疗提供了理论依据。另外，在探讨其信号通路与靶点的基础上，为未来在糖尿病靶向治疗上进行新颖有效的干预策略或药物开发提供新的思路。

糖尿病严重影响着人们健康与生活, 运动有益于其预防、控制与治疗, 但作用机制尚不明确。本研究基于糖尿病具有Irisin水平低下、细胞自噬功能缺陷等特点, 以STZ诱导的II型糖尿病大鼠或db/db小鼠为研究对象，对运动干预后STZ诱导的II型糖尿病大鼠或db/db小鼠血糖、Irisin、miR-143等指标的测定；肝脏组织内线粒体与自噬溶酶体的电镜观察；细胞自噬、细胞凋亡、胰岛素抵抗、线粒体质量控制相关蛋白的Western bot评估；同时，运用外源性Irisin、p38抑制剂SBSB203580、miR-143抑制剂从正反两方面进行探讨并确立了Irisin介导的miR-143调控细胞自噬功能状态以改善胰岛素抵抗与II型糖尿病的缓解作用，探明了运动干预II型糖尿病的精准信号通路或靶点。本研究首次提出了运动诱导Irisin与 miR-143介导的细胞自噬功能状态在控制血糖水平、改善胰岛素抵抗、维持内环境稳定、预防与治疗糖尿病中的作用, 为糖尿病预防与治疗提供了理论依据。另外，在探讨其精准信号通路与靶点的基础上，为未来在糖尿病靶向治疗上进行新颖有效的干预策略或运动模拟物开发提供新的思路。