Chinese bayberry (Myrica rubra Sieb. et Zucc.) leaves proanthocyanidins alleviate insulin-resistance via activating PI3K/AKT pathway in HepG2 cells

Chinese bayberry (Myrica rubra Sieb. et Zucc.) leaves proanthocyanidins (BLPs) were natural bioactive compounds in the treatment of obesity and diabetes with a unique structural characteristic. This study aimed to investigate the effect of BLPs on hepatic glucose metabolism in insulin-resistant HepG2 cells and elucidate the underlying mechanism. With the supplementation of BLPs, the glucose consumption and glucose uptake in IR-HepG2 cells were increased. BLPs promoted glycogen synthesis via up-regulating p-GSK3β and GYS2 expression, and attenuated gluconeogenesis by down-regulating PEPCK and G6Pase expression. It was attributed to the activation of PI3K/AKT signal pathway by BLPs, which was confirmed using the PI3K inhibitor LY294002. Moreover, BLPs remarkably reduced the expression of miR-29a, miR-423 and miR-122, which involved in hepatic glucose metabolism. Our results provide an insight of the hypoglycemic potential of BLPs on the hepatic glucose metabolism, suggesting that BLPs can be further used as a novel ingredient in functional food.