[Effects of ursolic acid in ameliorating insulin resistance in liver of KKAy mice via peroxisome proliferator-activated receptors α and γ].
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).


CONCLUSIONS
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.
Department of Traditional Chinese Medicine, Changhai Hospital, Second Military Medical University, Shanghai, China.
Lin
L
Wang
Guan-liang
GL
Wang
Jia-han
JH
Liu
Di
D
Li
De-zeng
DZ
Zhu
Liang-neng
LN
Wu
D052242:Adiponectin / Q000378:metabolism; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004195:Disease Models, Animal; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007333:Insulin Resistance; D008099:Liver / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D047493:PPAR alpha / Q000187:drug effects*; D047495:PPAR gamma / Q000378:metabolism; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology; D014315:Triterpenes / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000097245:Ursolic Acid
D052242:Adiponectin; D007004:Hypoglycemic Agents; D047493:PPAR alpha; D047495:PPAR gamma; D000077154:Rosiglitazone; D045162:Thiazolidinediones; D014315:Triterpenes; D014409:Tumor Necrosis Factor-alpha; D000097245:Ursolic Acid; C499919:Adipoq protein, mouse