Resveratrol metabolites ameliorate insulin resistance in HepG2 hepatocytes by modulating IRS-1/AMPK

Wendi Teng; Wenjing Yin; Liang Zhao; Changwei Ma; Jiaqiang Huang; Fazheng Ren

doi:10.1039/c8ra05092a

Resveratrol metabolites ameliorate insulin resistance in HepG2 hepatocytes by modulating IRS-1/AMPK

RSC Adv. 2018 Oct 23;8(63):36034-36042. doi: 10.1039/c8ra05092a. eCollection 2018 Oct 22.

Authors

Wendi Teng^{1

2}, Wenjing Yin^{1

2}, Liang Zhao^{1

2

3}, Changwei Ma^{1

2

3}, Jiaqiang Huang^{1

2

3}, Fazheng Ren^{1

2

3}

Affiliations

¹ 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 renfazheng@cau.edu.cn +86-10-62736344.
² 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.
³ Beijing Higher Institution Engineering Research Center of Animal Product, College of Food Science & Nutritional Engineering, China Agricultural University Beijing China.

Abstract

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.