Ginsenoside Rg3 ameliorates myocardial glucose metabolism and insulin resistance via activating the AMPK signaling pathway.

Ginsenoside Rg3 ameliorates myocardial glucose metabolism and insulin resistance via activating the AMPK signaling pathway.
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人参皂苷 Rg3 通过激活 AMPK 信号通路改善心肌葡萄糖代谢和胰岛素抵抗

DOI:
10.1016/j.jgr.2021.06.001
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发表时间:
2022-03
影响因子:
6.3
通讯作者:
Fan, Guanwei
Fan, Guanwei
中科院分区:
医学2区
文献类型:
--
作者:
Ni, Jingyu;Liu, Zhihao;Jiang, Miaomiao;Li, Lan;Deng, Jie;Wang, Xiaodan;Su, Jing;Zhu, Yan;He, Feng;Mao, Jingyuan;Gao, Xiumei;Fan, Guanwei

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人参皂甙Rg 3是人参中的主要活性成分之一。本研究旨在证实其对横主动脉缩窄(TAC)诱导的心力衰竭小鼠心功能的保护作用,并探讨其可能的分子机制。通过治疗TAC诱导的心力衰竭小鼠,研究了Rg 3对心脏和线粒体功能的影响。通过蛋白质组学和血浆代谢组学的综合分析,预测了Rg 3改善心力衰竭小鼠心脏和线粒体功能的机制。采用微量正电子发射断层扫描评价葡萄糖摄取和心肌胰岛素敏感性。结合在体动物实验和体外细胞实验,阐明了Rg 3对心肌胰岛素敏感性的影响。TAC-Rg 3治疗TAC诱导的小鼠模型显著改善了心脏功能,保护了线粒体结构和功能。代谢组学、蛋白质组学和靶向代谢组学数据的融合表明,Rg 3调节糖酵解过程,Rg 3不仅调节葡萄糖摄取,而且改善心肌胰岛素抵抗。通过探讨AMPK、胰岛素抵抗和糖代谢的相互作用途径,确定了AMPRg 3调节糖代谢的分子机制。Rg 3通过激活AMPK促进IR-H9 c2细胞葡萄糖摄取的作用依赖于胰岛素信号通路。人参皂苷Rg 3通过激活AMPK通路调节葡萄糖代谢并显著改善胰岛素抵抗。
Ginsenoside Rg3 is one of the main active ingredients in ginseng. Here, we aimed to confirm its protective effect on the heart function in transverse aortic coarctation (TAC)-induced heart failure mice and explore the potential molecular mechanisms involved. The effects of ginsenoside Rg3 on heart and mitochondrial function were investigated by treating TAC-induced heart failure in mice. The mechanism of ginsenoside Rg3 for improving heart and mitochondrial function in mice with heart failure was predicted through integrative analysis of the proteome and plasma metabolome. Glucose uptake and myocardial insulin sensitivity were evaluated using micro-positron emission tomography. The effect of ginsenoside Rg3 on myocardial insulin sensitivity was clarified by combining in vivo animal experiments and in vitro cell experiments. Treatment of TAC-induced mouse models with ginsenoside Rg3 significantly improved heart function and protected mitochondrial structure and function. Fusion of metabolomics, proteomics, and targeted metabolomics data showed that Rg3 regulated the glycolysis process, and Rg3 not only regulated glucose uptake but also improve myocardial insulin resistance. The molecular mechanism of ginsenoside Rg3 regulation of glucose metabolism was determined by exploring the interaction pathways of AMPK, insulin resistance, and glucose metabolism. The effect of ginsenoside Rg3 on the promotion of glucose uptake in IR-H9c2 cells by AMPK activation was dependent on the insulin signaling pathway. Ginsenoside Rg3 modulates glucose metabolism and significantly ameliorates insulin resistance through activation of the AMPK pathway.
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