Peroxisome proliferator-activated receptor gamma transactivation-mediated potentiation of glucose uptake by Bai-Hu-Tang

ETHNOPHARMACOLOGICAL RELEVANCE: The molecular mechanism of a traditional hypoglycemic Chinese herbal formula. AIM OF THE STUDY: To explore the glucose uptake effect as well as the mechanism(s) of action of Bai-Hu-Tang (BHT), a traditional Chinese herbal formula, composed of anemarrhena, gypsum, licorice and rice. MATERIALS AND METHODS: Differentiated 3T3-L1 adipocytes were treated with vehicle, insulin or insulin plus different concentrations of BHT. The 2-deoxy-(3)H] glucose uptake assay was performed to measure the amount of glucose uptake. To explore the mechanism(s) of glucose uptake of BHT, we used two insulin signaling transduction inhibitors, N-Acetyl-Leu-Leu-Norleu-al (ALLN), a calpain inhibitor, and LY 294002, a phosphatidylinositol (PI)3-kinase inhibitor, to test if the glucose uptake effect was mediated by the insulin signaling pathway. We then used Western blot analysis to re-confirm the result of the insulin signaling inhibition assay. Finally, reporter chimera assay of HuH-7 cells was used to measure the peroxisome proliferator-activated receptor gamma (PPARgamma) activation by BHT. RESULTS: BHT potentiated insulin-stimulated glucose uptake in 3T3-L1 adipocytes. The effect of BHT-stimulated glucose uptake was neither inhibited by ALLN nor by LY 294002. The protein expression of PI3 kinase pathway did not change after BHT stimulation. PPARgamma activation was elevated by 67.7+/-32% (p<0.05) in HuH-7 cells treated with 0.8 microg/ml of BHT. CONCLUSIONS: BHT stimulated glucose uptake in 3T3-L1 adipocytes. This effect was via PPARgamma activation rather than via the insulin signaling pathway.