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Panax ginseng is known to have anti-diabetic activity, but the active ingredients are not yet fully identified. In this study, we found the inhibitory effect of Rg1 on hepatic glucose production through AMP-activated protein kinase (AMPK) activation in HepG2 cells. Rg1 significantly inhibited hepatic glucose production in a concentration-dependent manner, and this effect was reversed in the presence of compound C, a selective AMPK inhibitor. In addition, Rg1 markedly induced the phosphorylations of liver kinase B1 (LKB1), AMPK and forkhead box class O1 (FoxO1), a key transcription factor for gluconeogenic enzymes, in time- and concentration-dependent manners. Glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK) activities were inhibited by 24% and 21%, respectively, when the cells were exposed to 40 μM of Rg1, resulting from phosphorylation of FoxO1 and inhibition of gluconeogenic gene expression. Taken together, our results demonstrated the suppressive effect of Rg1 on hepatic glucose production via LKB1-AMPK-FoxO1 pathway in HepG2 human hepatoma cells.
- Biological and Pharmaceutical Bulletin
Biological and Pharmaceutical Bulletin 33(2), 325-328, 2010
The Pharmaceutical Society of Japan