Teng Wendi, Yin Wenjing, Zhao Liang, Ma Changwei, Huang Jiaqiang, Ren Fazheng
Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science & Nutritional Engineering, China Agricultural University P.O. Box 287, No. 17 Qinghua East Road Beijing 100083 China
Key Laboratory of Functional Dairy, Co-constructed by Ministry of Education and Beijing Municipality, College of Food Science & Nutritional Engineering, China Agricultural University Beijing China.
RSC Adv. 2018 Oct 23;8(63):36034-36042. doi: 10.1039/c8ra05092a. eCollection 2018 Oct 22.
Resveratrol (-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--glucuronide (R3G) and RSV-4--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 mol L 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 , RSV biological effects could be mediated through its metabolites.
白藜芦醇（-3,5,4'-三羟基茋，RSV）是一种天然存在的具有生物活性的多酚，已观察到它在糖尿病动物和人类中能产生多种有益作用。然而，由于其低生物利用度和快速清除率，其保护作用存在一定争议。因此，在本研究中，我们试图探究其主要代谢产物RSV - 3 - β - 葡萄糖醛酸苷（R3G）和RSV - 4 - β - 葡萄糖醛酸苷（R4G）是否能改善胰岛素抵抗，类似于RSV对胰岛素抵抗的HepG2细胞的作用。在此，我们首先通过用1×10⁻⁶ mol/L胰岛素处理HepG2细胞24小时建立了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处理改善了细胞葡萄糖摄取和糖原合成含量，并阻止了细胞内活性氧（ROS）的产生。此外，R3G和R4G还通过调节IRS - 1/AMPK信号通路调节胰岛素信号并提高胰岛素敏感性。综上所述，我们的数据为R3G和R4G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，我们的数据支持了这样一种假设，即尽管生物利用度低，但RSV的生物学效应可能通过其代谢产物介导。
