Ginsenoside Rg3 ameliorates myocardial glucose metabolism and insulin resistance via activating the AMPK signaling pathway,Journal of Ginseng Research

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Ginsenoside Rg3 ameliorates myocardial glucose metabolism and insulin resistance via activating the AMPK signaling pathway
Journal of Ginseng Research ( IF 6.8 ) Pub Date : 2021-06-05 , DOI: 10.1016/j.jgr.2021.06.001
Jingyu Ni _{1,

2} , Zhihao Liu ₁ , Miaomiao Jiang ₃ , Lan Li ₁ , Jie Deng ₁ , Xiaodan Wang ₁ , Jing Su ₃ , Yan Zhu ₃ , Feng He ₂ , Jingyuan Mao ₁ , Xiumei Gao ₃ , Guanwei Fan _{1,

2,

3}

Affiliation

Background

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.

Methods

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.

Results

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.

Conclusions

Ginsenoside Rg3 modulates glucose metabolism and significantly ameliorates insulin resistance through activation of the AMPK pathway.

中文翻译：

人参皂甙Rg3通过激活AMPK信号通路改善心肌糖代谢和胰岛素抵抗

背景

人参皂甙Rg3是人参的主要活性成分之一。在这里，我们旨在确认其对横向主动脉缩窄 (TAC) 诱导的心力衰竭小鼠心脏功能的保护作用，并探索其潜在的分子机制。

方法

通过治疗 TAC 诱导的小鼠心力衰竭，研究了人参皂甙 Rg3 对心脏和线粒体功能的影响。通过蛋白质组和血浆代谢组的综合分析，预测了人参皂甙 Rg3 改善心力衰竭小鼠心脏和线粒体功能的机制。使用微正电子发射断层扫描评估葡萄糖摄取和心肌胰岛素敏感性。通过体内动物实验和体外细胞实验相结合，阐明了人参皂甙Rg3对心肌胰岛素敏感性的影响。

结果

用人参皂苷 Rg3 治疗 TAC 诱导的小鼠模型可显着改善心脏功能并保护线粒体结构和功能。代谢组学、蛋白质组学和靶向代谢组学数据的融合表明，Rg3 调节糖酵解过程，Rg3 不仅调节葡萄糖摄取，而且改善心肌胰岛素抵抗。通过探索AMPK、胰岛素抵抗和糖代谢的相互作用途径，确定了人参皂苷Rg3调节糖代谢的分子机制。人参皂甙 Rg3 通过 AMPK 激活促进 IR-H9c2 细胞摄取葡萄糖的作用依赖于胰岛素信号通路。