Effect of ursolic acid on obesity-induced insulin resistance in rat liver
Purpose: To determine the expression of protein tyrosine phosphatase-1B (PTP-1B) and insulin receptor substrate-2 (IRS-2) in the liver tissue of obesity-induced insulin-resistant rats.
Methods: Insulin resistance (IR) was induced in Wistar rats by placing them on a high fat diet for 6weeks, and ursolic acid (UA) was administered. Metformin served as positive control drug. The rats were divided into 5 groups based on the treatments given: normal group, positive control group, metformin group, high-dose UA group, and low-dose UA group. The general conditions of the rats were assessed 4 and 8 weeks after the various treatments. Liver glycogen levels were measured, and liver histological examination carried out after tissue processing and staining with hematoxylin and eosin (H & E). Real-time polymerase chain reaction (RT-PCR) was employed for the determination of hepatic expressions of PTP-1B and IRS-2 mRNAs, while expressions of PTP-1B protein and IRS-2 protein, and phosphorylation of IRS-2 tyrosine were assayed by Western blotting.
Results: Liver glycogen levels were significantly increased in the UA-treated groups (p < 0.05). Moreover, UA provoked reductions in the expression of PTP-1B protein (p < 0.05), but up-regulated the expression of IRS-2 protein (p < 0.05), and enhanced IRS-2 tyrosine phosphorylation (p < 0.05).
Conclusion: These results suggest that UA mitigates IR through blockage of PTP-1B expression and up-regulation of the expression of IRS-2 mRNA. Therefore, PTP-1B is a potential target for the treatment of type 2 diabetes.
Keywords: Ursolic acid, Insulin resistance, Liver, Protein tyrosine phosphatase-1B, Insulin receptor substrate-