%A Lin Wang, Guan-liang Wang, Jia-han Liu, Di Li, De-zeng Zhu, Liang-neng Wu %T Effects of ursolic acid in ameliorating insulin resistance in liver of KKAy mice via peroxisome proliferator-activated receptors α and γ %0 Journal Article %D 2012 %J Journal of Integrative Medicine %R 10.3736/jcim20120710 %P 793-799 %V 10 %N 7 %U {http://www.jcimjournal.com/CN/abstract/article_1135.shtml} %8 2012-07-20 %X

Objective: To explore the effects and mechanism of ursolic acid in improving hepatic insulin resistance in KKAy mice with spontaneous type 2 diabetes.
Methods: Thirty-five KKAy mice were divided into five groups according to the randomized block design, namely, control, rosiglitazone, fenofibrate, and high- and low-dose ursolic acid groups with seven mice in each group. C57BL/6J mice were used as the normal control group. At the end of the 4th week, free fatty acid (FFA), tumor necrosis factor-α (TNF-α) and adiponectin contents in serum were detected by enzyme-linked immunosorbent assay; the protein expressions of phosphoenolpyruvate carboxykinase (PEPCK), insulin receptor substrate-2 (IRS-2) and glucose transport factor-2 (GLUT-2) were detected by Western blot method; the mRNA expressions of PEPCK, IRS-2 and GLUT-2 were detected by real-time polymerase chain reaction; the expressions of peroxisome proliferator-activated receptor α (PPARα) and peroxisome proliferator-activated receptor γ (PPARγ) in liver tissue were detected by immunohistochemical method.
Results: After four weeks of intervention, the contents of FFA, TNF-α and adiponectin in serum of the high-dose ursolic acid group had changed, showing statistically significant difference compared to those of the control group (P<0.01); high dose of ursolic acid had depressant effect on the expressions of PEPCK protein and PEPCK mRNA (P<0.01); low dose of ursolic acid depressed the expression of PEPCK mRNA and induced phosphorylation of IRS-2 in the liver (P<0.05); both high and low dose of ursolic acid improved the expression of PPARα in the liver (P<0.01).
Conclusion: The effects of ursolic acid in improving hepatic insulin resistance in KKAy mice with spontaneous type 2 diabetes may be closely related to affecting the contents of FFA, TNF-α and adiponectin, improving the expression of PPARα protein, regulating transcription of PEPCK protein and inducing phosphorylation of IRS-2.