Ginsenoside Rg1 suppresses hepatic glucose production via AMP-activated protein kinase in HepG2 cells.
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 Rg(1) on hepatic glucose production through AMP-activated protein kinase (AMPK) activation in HepG2 cells. Rg(1) 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, Rg(1) 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 microM of Rg(1), resulting from phosphorylation of FoxO1 and inhibition of gluconeogenic gene expression. Taken together, our results demonstrated the suppressive effect of Rg(1) on hepatic glucose production via LKB1-AMPK-FoxO1 pathway in HepG2 human hepatoma cells.
Kim
Sung Jip
SJ
Department of Life and Nanopharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul 130-701, Republic of Korea.
Yuan
Hai Dan
HD
Chung
Sung Hyun
SH
D055372:AMP-Activated Protein Kinases / Q000502:physiology*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D036145:Ginsenosides / Q000494:pharmacology*; D005943:Gluconeogenesis / Q000187:drug effects / Q000502:physiology; D005947:Glucose / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D005894:Panax
D004365:Drugs, Chinese Herbal; D036145:Ginsenosides; D055372:AMP-Activated Protein Kinases; D005947:Glucose; C035054:ginsenoside Rg1