search button
Open Access

Sitagliptin inhibits endothelin-1 expression in the aortic endothelium of rats with streptozotocin-induced diabetes by suppressing the nuclear factor-κB/IκBα system through the activation of AMP-activated protein kinase

  • Authors:
    • Song-Tao Tang
    • Huan Su
    • Qiu Zhang
    • Hai-Qin Tang
    • Chang-Jiang Wang
    • Qing Zhou
    • Wei Wei
    • Hua-Qing Zhu
    • Yuan Wang

  • View Affiliations

  • Published online on: April 26, 2016     https://doi.org/10.3892/ijmm.2016.2578
  • Pages: 1558-1566

  • Copyright: © Tang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Emerging evidence suggests that dipeptidyl peptidase-4 (DPP-4) inhibitors, including sitagliptin, exert favourable effects on the vascular endothelium. DPP-4 inhibitors suppress the degradation of glucagon-like peptide-1 (GLP‑1), which has been reported to enhance nitric oxide (NO) production. However, the effects of DPP-4 inhibitors on endothelin-1 (ET-1) expression in the aorta, as well as the underlying mechanisms responsible for these effects, have yet to be investigated in animal models of diabetes mellitus (DM). In the present study, the rats were randomly divided into the following four groups: i) control; ii) DM; iii) DM + low‑dose sitagliptin (10 mg/kg); and iv) DM + high‑dose sitagliptin (30 mg/kg). Apart from the control group, all the rats received a high-fat diet for 8 weeks prior to the induction of diabetes with an intraperitoneal injection of streptozotocin. The treatments were then administered for 12 weeks. The serum levels of ET-1, NO, GLP-1 and insulin were measured as well as endothelial function. The expression of ET-1, AMP-activated protein kinase (AMPK) and nuclear factor (NF)-κB/IκBα were determined. After 12 weeks of treatment, the diabetic rats receiving sitagliptin showed significantly elevated serum levels of GLP-1 and NO, and reduced levels of ET-1. Moreover, sitagliptin significantly attenuated endothelial dysfunction as well as the remodeling of the aortic wall. Notably, sitagliptin inhibited ET-1 expression at the transcriptional and translational level in the aorta, which may have been mediated by the suppression of the NF-κB/IκBα system induced by AMPK activation. The majority of the above-mentioned effects were dose dependent. Taken together, the findings of the present study indicate that sitagliptin inhibits ET-1 expression in the aortic endothelium by suppressing the NF-κB/IκBα system through the activation of the AMPK pathway in diabetic rats. These findings further demonstrate some of the vasoprotective properties of DPP-4 inhibitors in vivo.
View Figures
View References

Related Articles

Journal Cover

June-2016
Volume 37 Issue 6

Print ISSN: 1107-3756
Online ISSN:1791-244X

Sign up for eToc alerts

Recommend to Library

  • Journal Metrics
  • Impact Factor: 5.4
  • Ranked Medicine Research and Experimental
    (total number of cites)
  • CiteScore: 10.7
  • CiteScore Rank: Q1: #35/328 Biochemistry, Genetics and Molecular Biology
  • Source Normalized Impact per Paper (SNIP): 0.994
  • SCImago Journal Rank (SJR): 0.922
International Symposium on Molecular Medicine Conference Banner
The Cancer Story
World Congress on Advances in Oncology and International Symposium on Molecular Medicine Conference Banner
World Academy Of Sciences Banner
Heyday Road Banner

0

Copy and paste a formatted citation
x
Spandidos Publications style
Tang S, Su H, Zhang Q, Tang H, Wang C, Zhou Q, Wei W, Zhu H and Wang Y: Sitagliptin inhibits endothelin-1 expression in the aortic endothelium of rats with streptozotocin-induced diabetes by suppressing the nuclear factor-κB/IκBα system through the activation of AMP-activated protein kinase. Int J Mol Med 37: 1558-1566, 2016
APA
Tang, S., Su, H., Zhang, Q., Tang, H., Wang, C., Zhou, Q. ... Wang, Y. (2016). Sitagliptin inhibits endothelin-1 expression in the aortic endothelium of rats with streptozotocin-induced diabetes by suppressing the nuclear factor-κB/IκBα system through the activation of AMP-activated protein kinase. International Journal of Molecular Medicine, 37, 1558-1566. https://doi.org/10.3892/ijmm.2016.2578
MLA
Tang, S., Su, H., Zhang, Q., Tang, H., Wang, C., Zhou, Q., Wei, W., Zhu, H., Wang, Y."Sitagliptin inhibits endothelin-1 expression in the aortic endothelium of rats with streptozotocin-induced diabetes by suppressing the nuclear factor-κB/IκBα system through the activation of AMP-activated protein kinase". International Journal of Molecular Medicine 37.6 (2016): 1558-1566.
Chicago
Tang, S., Su, H., Zhang, Q., Tang, H., Wang, C., Zhou, Q., Wei, W., Zhu, H., Wang, Y."Sitagliptin inhibits endothelin-1 expression in the aortic endothelium of rats with streptozotocin-induced diabetes by suppressing the nuclear factor-κB/IκBα system through the activation of AMP-activated protein kinase". International Journal of Molecular Medicine 37, no. 6 (2016): 1558-1566. https://doi.org/10.3892/ijmm.2016.2578