Berbenne-stimulated glucose uptake in L6 myotubes involves both AMPK and p38 MAPK

Berberine is a plant alkaloid used in traditional Chinese medicine and has been reported to have antihyperglycemic activity in NIDDM patients.However, the molecular basis for this action is yet to be elucidated. Here we investigate the effects and signaling pathways of berberine on L6 rat skeletal muscles. Our study demonstrates that berberine stimulates glucose uptake in a time- and dose-dependent manner. Intriguingly, berberine-stimulated glucose uptake does not vary as insulin concentration increases, and could not be blocked by the PI 3-kinase inhibitor wortmannin.Berberine only weakly stimulates the phosphorylation of Akt/PKB, a key molecule in the insulin signaling pathway, but strongly promotes the phosphorylation of AMPK and p38 MAPK. The effects of berberine are not a result of pro-oxidant action, but a consequence of an increased cellular AMP:ATP ratio. Moreover, berberine-stimulated glucose uptake is inhibited by the AMPK inhibitor Compound C and the p38 MAPK inhibitor SB202190. Inhibition of AMPK reduces p38 MAPK phosphorylation, suggesting that AMPK lies upstream of p38 MAPK. These results suggest that berberine circumvents insulin signaling pathways and stimulates glucose uptake through the AMP-AMPK-p38 MAPK pathway,which may account for the antihyperglycemic effects of this drug.
Berberine Glucose uptake AMPK p38 MAPK Myotube
Zhe Cheng Tao Pang Min Gu An-Hui Gao Chuan-Ming Xie Jing-Ya Li Fa-Jun Nan Jia Li
National Center for Drug Screening, Shanghai Institute of Materia Uedica, Shanghai Institutes for Biological Sciences,Chinese Academy of Sciences, Shanghai 201203, P.R.China
国际会议
南京
英文
13-20
2009-09-11(万方平台首次上网日期,不代表论文的发表时间)