Ginsenoside Rg5 Improves Insulin Resistance and Mitochondrial Biogenesis of Liver via Regulation of the Sirt1/PGC-1α Signaling Pathway in db/db Mice
Ginsenoside Rg5 Improves Insulin Resistance and Mitochondrial Biogenesis of Liver via Regulation of the Sirt1/PGC-1α Signaling Pathway in db/db Mice
复制标题
人参皂苷 Rg5 通过调节 db/db 小鼠的 Sirt1/PGC-1 α 信号通路改善胰岛素抵抗和肝脏线粒体生物发生
DOI：
10.1021/acs.jafc.1c02476
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发表时间：
2021-07-26
影响因子：
6.1
通讯作者：
Fan, Daidi
中科院分区：
文献类型：
--
作者：
Zhu, Yanyan;Yang, Haixia;Fan, Daidi
2型糖尿病（T2 DM）是一种常见的代谢综合征，可降低胰岛素敏感性和肝脏线粒体生物合成。我们以前的研究表明，Rg 5可以减轻糖尿病小鼠的肾损伤，但其在线粒体生物合成和胰岛素敏感性方面的潜在机制仍然知之甚少。在本研究中，我们发现Rg 5干预显著抑制db/db小鼠血糖升高，改善肝功能损害和肝细胞凋亡，并激活IRS-1/磷脂酰肌醇3-激酶/AKT胰岛素代谢信号通路。Rg 5处理还增加了糖原合成水平和激活sirtuin 1（Sirt 1），以增加胰岛素抵抗HepG 2（IR-HepG 2）细胞的葡萄糖摄取和胰岛素敏感性。Rg 5干预还有效地改善db/db小鼠的肝脏氧化应激和炎症，并增加由T2 DM引起的线粒体生物合成。此外，Rg 5处理增加了IR-HepG 2细胞中的线粒体质量，并激活了Sirt 1以调节Sirt 1/PGC-1 α/mitofusin-2线粒体生物合成途径。我们的研究结果表明，Rg 5通过激活Sirt 1/PGC-1 α信号通路增强db/db小鼠的肝脏线粒体生物合成和胰岛素敏感性，表明Rg 5作为T2 DM干预的天然产物的潜力。
Type 2 diabetes mellitus (T2DM) is a common metabolic syndrome that decreases insulin sensitivity and mitochondrial biogenesis in the liver. Our previous study demonstrated that ginsenoside Rg5 (Rg5) could attenuate renal injury in diabetic mice but its underlying mechanism in mitochondrial biogenesis and insulin sensitivity remains poorly understood. In this study, we found that Rg5 intervention significantly inhibited blood glucose increases in db/db mice, improved liver function damage and hepatocyte apoptosis, and activated the IRS-1/phosphatidylinositol 3-kinase/AKT insulin metabolism signaling pathway. Rg5 treatment also increased the level of glycogen synthesis and activated sirtuin1 (Sirt1) to increase glucose uptake and insulin sensitivity in insulin-resistant HepG2 (IR-HepG2) cells. Rg5 intervention also effectively improved liver oxidative stress and inflammation in db/db mice and increased mitochondrial biogenesis caused by T2DM. Additionally, the Rg5 treatment increased the mitochondrial mass in IR-HepG2 cells and activated Sirt1 to regulate the Sirt1/PGC-1 alpha/mitofusin-2 mitochondrial biosynthesis pathway. Our findings demonstrated that Rg5 enhanced liver mitochondrial biogenesis and insulin sensitivity in db/db mice by activating the Sirt1/PGC-1 alpha signaling pathway, suggesting the potential of Rg5 as a natural product for T2DM interventions.