Ginsenoside Rc, an active component of Panax ginseng, stimulates glucose uptake in C2C12 myotubes through an AMPK-dependent mechanism

Ethnopharmacological relevance: Panax ginseng and its major component, ginsenosides, are widely used for the prevention of various disorders in oriental medicine. Aim of the study: To evaluate the effect of ginsenoside Rc (Rc), one of the active constituents in Panax ginseng, on glucose uptake in C2C12 myotubes. Results: Treatment of the C2C12 myotubes with Rc significantly increased glucose uptake. To determine the mechanism of Rc-induced glucose uptake, either insulin-dependent signaling or insulin-independent signaling pathway activities were measured using western blot analysis. We showed that Rc significantly activated an insulin-independent AMPK signaling pathway. However, Rc had no effect on the components of the insulin-dependent signaling pathway, such as receptor substrates (IRS)-1 and protein kinase B or Akt (PKB/Akt). Moreover, we found that treatment with an AMPK inhibitor abolished both glucose uptake and p38 MAPK phosphorylation. This result implies that AMPK activity is critical for the Rc-induced glucose uptake and that AMPK is situated upstream of p38 MAPK. In addition, we also showed that the activation of AMPK and p38 induced by ginsenoside Rc is mediated by reactive oxygen species (ROS) production, suggesting that upstream regulators of AMPK- and p38 MAPK-mediated glucose uptake. Conclusion: Ginsenoside Rc significantly enhances glucose uptake by inducing ROS generation, which leads to AMPK and p38 MAPK activation. Consequently, ginsenoside Rc can be used as a potent natural anti-diabetic agent. (C) 2009 Elsevier Ireland Ltd. All rights reserved.