Caffeic acid and cinnamic acid ameliorate glucose metabolism via modulating glycogenesis and gluconeogenesis in insulin-resistant mouse hepatocytes

Tumour necrosis factor-α (TNF-α) plays a pivotal role in cellular insulin resistance and can induce insulin resistance in mouse FL83B hepatocytes. Caffeic acid and cinnamic acid were found to improve glucose uptake in TNF-α-treated insulin-resistant mouse FL83B hepatocytes. The mechanism of glucose metabolism by caffeic acid and cinnamic acid was further investigated. The result from Western blot analysis revealed that caffeic acid and cinnamic acid increased expression of glycogen synthase, whereas the expression of glycogen synthase kinase and phosphorylation of glycogen synthase at Ser641 in insulin-resistant mouse hepatocytes was decreased. Caffeic acid and cinnamic acid suppressed the expression of hepatic nuclear factor-4 in TNF-α-treated mouse FL83B hepatocytes. The activity of phosphoenolpyruvate carboxykinase was also inhibited. Thus, caffeic acid and cinnamic acid ameliorated glucose metabolism by promoting glycogenesis and inhibiting gluconeogenesis in TNF-α-treated insulin-resistant mouse hepatocytes.