The molecular basis of the antidiabetic activity of quercetin in skeletal muscle cells and hepatocytes in culture
Quercetin is most abundant flavonoid in the human diet. In a previous study, we have reported that quercetin stimulated glucose uptake in cultured C2C12 skeletal muscle through an insulin-independent mechanism involving adenosine monophosphate-activated protein kinase (AMPK). In skeletal muscle, the activation of AMPK increases glucose uptake through the stimulation of glucose transporter GLUT4 translocation to the plasma membrane. In liver, AMPK decreases hepatic glucose production mainly through the downregulation of the key gluconeogenesis enzymes such as phosphoenolpyruvate carboxylase and Glucose 6-phosphate (G6Pase). In the present study, an 18h treatment with quercetin (50µM) was reported to stimulate AMPK and to increase GLUT4 translocation and expression in cultured rat L6 skeletal muscle cells. On the other hand, we reported that quercetin induced hepatic AMPK activation and inhibited G6pase in murine H4IIE hepatocytes. Finally, we have observed that querectin exhibited a mild tendency to increase the activity of glycogen synthase (GS), the rate-limiting enzyme of glycogen synthesis, in the human hepatoma cell line HepG2. Overall, these data demonstrate that quercetin positively influences glucose metabolism in both liver and skeletal muscle, and therefore appear to be a promising therapeutic candidate for the treatment of type 2 diabetes mellitus.