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首页> 外文期刊>RSC Advances >Resveratrol metabolites ameliorate insulin resistance in HepG2 hepatocytes by modulating IRS-1/AMPK
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Resveratrol metabolites ameliorate insulin resistance in HepG2 hepatocytes by modulating IRS-1/AMPK

机译：白藜芦醇代谢物通过调节IRS-1 / AMPK改善HepG2肝细胞的胰岛素抵抗

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Resveratrol ( trans -3,5,4′-trihydroxystilbene, RSV), a naturally occurring biologically active polyphenol has been observed to induce numerous beneficial effects in diabetic animals and humans. However, its protective effects are somewhat controversial due to low bioavailability and rapid clearance rate. Therefore, we in this study have tried to investigate if its main metabolites, RSV-3- O -glucuronide (R3G) and RSV-4- O -glucuronide (R4G) could ameliorate insulin resistance, similar to RSV in insulin-resistant HepG2 cells. Herein, we first established an insulin-resistant cell model by treating HepG2 cells with 1 × 10 ~(?6) mol L ~(?1) insulin for 24 h. Subsequently, the effects of R3G and R4G on insulin resistance inhibition were evaluated in HepG2 cells. Interestingly, our data indicated that R3G and R4G treatment improved cellular glucose uptake and glycogen synthesis contents, and blocked generation of intracellular reactive oxygen species (ROS). Additionally, R3G and R4G also modulated insulin signaling and improved insulin sensitivity by modulating the IRS-1/AMPK signaling pathway. Taken together, our data provided a significant new insight into the effects and molecular mechanism of R3G and R4G on ameliorating insulin resistance in HepG2 cells. Overall, our data supported the hypothesis that despite low bioavailability in vivo , RSV biological effects could be mediated through its metabolites.
机译：已经观察到白藜芦醇（反式-3,5,4'-三羟基V，RSV），一种天然存在的生物活性多酚，可在糖尿病动物和人类中诱导多种有益作用。然而，由于其生物利用度低和清除率高，其保护作用尚存在争议。因此，我们在这项研究中试图研究其主要代谢产物RSV-3-O-葡萄糖醛酸（R3G）和RSV-4-O-葡萄糖醛酸（R4G）是否可以改善胰岛素抵抗，类似于胰岛素抵抗HepG2细胞中的RSV。 。在此，我们首先通过用1×10〜（？6）mol L〜（？1）胰岛素处理HepG2细胞24小时来建立胰岛素抵抗细胞模型。随后，在HepG2细胞中评估了R3G和R4G对胰岛素抵抗抑制的作用。有趣的是，我们的数据表明R3G和R4G处理可改善细胞葡萄糖的摄取和糖原合成的含量，并阻止细胞内活性氧（ROS）的产生。此外，R3G和R4G还通过调节IRS-1 / AMPK信号传导途径来调节胰岛素信号传导并改善胰岛素敏感性。综上所述，我们的数据为R3G和R4G对改善HepG2细胞胰岛素抵抗的作用和分子机制提供了重要的新见解。总体而言，我们的数据支持以下假说：尽管体内生物利用度低，RSV的生物学效应仍可以通过其代谢产物介导。

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