Effect of ursolic acid on obesity-induced insulin resistance in rat liver
Abstract
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-
Submission of a manuscript to this journal is a representation that the manuscript has not been published previously and is not under consideration for publication elsewhere.
All authors named in each manuscript would be required to sign a form (to be supplied by the Editor) so that they may retain their copyright in the article but to assign to us (the Publishers) and its licensees in perpetuity, in all forms, formats and media (whether known or created in the future) to (i) publish, reproduce, distribute, display and store the contribution, (ii) translate the contribution into other languages, create adaptations, reprints, include within collections and create summaries, extracts and/or abstracts of the contribution, (iii) create any other derivative works(s) based on the contribution, (iv) to exploit all subsidiary rights in the contribution, (v) the inclusion of electronic links from the contribution to third party material where-ever it may be located, and (vi) license any thrid party to do any or all of the above.