Anti-insulin resistance effects of salidroside through mitochondrial quality control.
Anti-insulin resistance effects of salidroside through mitochondrial quality control.
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DOI：
10.1530/joe-19-0393
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发表时间：
2019-12
期刊：
影响因子：
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通讯作者：
Baiyang You;Yaoshan Dun;Wenliang Zhang;Ling Jiang;Hui Li;Murong Xie;Yuan Liu;Suixin Liu
中科院分区：
文献类型：
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作者：
Baiyang You;Yaoshan Dun;Wenliang Zhang;Ling Jiang;Hui Li;Murong Xie;Yuan Liu;Suixin Liu
线粒体质量控制（MQC）和功能是细胞能量代谢的决定因素，其紊乱在胰岛素抵抗（IR）的发生发展中起重要作用。据报道，红景天苷通过AMPK途径对MQC具有有益作用，然而，红景天苷是否通过该作用发挥抗IR作用尚不清楚。本研究旨在研究红景天苷对胰岛素抵抗的影响，并探讨其作用机制。实验IR模型分别采用高脂饮食（HFD）喂养的小鼠和棕榈酸酯处理的C2 C12肌管。测定葡萄糖和胰岛素的血液水平以及细胞葡萄糖摄取，基于用激活剂（AICAR）、抑制剂（化合物C和EX-527）或AMPK/SIRT 1的特异性siRNA和线粒体ROS清除剂（mito-TEMPO）的处理，分析线粒体功能和MQC相关参数以及活性氧（ROS）产生。蛋白质表达水平通过Western-Blot测定，细胞观察通过透射电子显微镜，活性氧产生通过功能分析试剂盒。红景天苷可降低IR，沿着激活胰岛素信号传导，并刺激AMPK/SIRT 1信号传导，调节MQC和ROS的产生。这些红景天苷的作用与AICAR的作用相当，并且可以分别通过AMPK/SIRT 1抑制剂或siRNA来预防。红景天苷通过激活AMPK/SIRT 1信号通路降低IR并调节MQC和ROS的产生。由于IR是公共卫生的关键问题，因此探索有效的抗IR剂具有很高的兴趣。红景天苷的抗IR作用值得进一步的实验和临床研究。
Mitochondrial quality control (MQC) and function are determinants for cellular energy metabolism and their disorders are reported to play important role in the development of insulin resistance (IR). Salidroside was reported to have beneficial effects on MQC through AMPK pathway, however, it is unknown whether salidroside exerts anti-IR effect with this action. This study sought to investigate effects of salidroside on IR with an exploration of the mechanisms of its action. Experimental IR models were adopted in high-fat diet (HFD) fed mice and palmitate-treated C2C12 myotubes, respectively. Blood levels of glucose and insulin as well as cellular glucose uptake were determined, mitochondrial function and MQC-associated parameters and reactive oxygen species (ROS) production were analyzed based on treatments with activator (AICAR), inhibitors (compound C and EX-527), or specific siRNA of AMPK/SIRT1 and mitochondrial ROS scavenger (mito-TEMPO). Protein expression level was determined by Western-Blot, cellular observation by transmission electron microscope, and ROS production by functional analysis kits. Salidroside reduced IR and activated insulin signaling along with stimulation of AMPK/SIRT1 signaling and downstream regulation of MQC and ROS production. These salidroside effects were comparable to those of AICAR and could be prevented by AMPK/SIRT1 inhibitors or siRNAs, respectively. Salidroside reduces IR and regulates MQC and ROS production through activating AMPK/SIRT1 signaling pathway. Since IR is a critical issue for public health, to explore a potent agent against IR is of high interest. The anti-IR effects of salidroside warrant further experimental and clinical studies.