Exendin‑4 inhibits lipotoxicity‑induced oxidative stress in β‑cells by inhibiting the activation of TLR4/NF‑κB signaling pathway

  • Authors:
    • Ximei Shen
    • Liufen Luo
    • Meng Yang
    • Yuxi Lin
    • Jing Li
    • Liyong Yang
  • View Affiliations

  • Published online on: February 6, 2020     https://doi.org/10.3892/ijmm.2020.4490
  • Pages: 1237-1249
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

The present study aimed to investigate the relationship between the protective effects of exendin‑4 (EX‑4) on lipotoxicity‑induced oxidative stress and meta‑inflammation in β‑cells and the toll‑like receptor 4 (TLR4)/NF‑κB signaling pathway. Lipotoxicity, hydrogen peroxide (H2O2)‑induced oxidative stress in β cells, obese Sprague Dawley rats and TLR4 truncation rats were utilized in the present study. The expression levels were detected by western blotting; cell apoptosis was detected by TUNEL assay; and the intracellular reactive oxygen species (ROS) levels were analyzed using a ROS assay kit. The findings of the present study showed that EX‑4 inhibited the expression of TLR4, NF‑κB p65 subunit and p47phox in a concentration‑dependent manner, and decreased the intracellular level of ROS. Additionally, silencing of TLR4 expression enhanced the protective effects of EX‑4, while overexpression of TLR4 attenuated these protective influences. Simultaneously, it was demonstrated that TLR4 was involved in the process of EX‑4 intervention to inhibit H2O2‑induced oxidative stress in islet β‑cells. Moreover, it was found that EX‑4 also inhibited TLR4‑ or NF‑κB agonist‑induced oxidative stress. These results were also confirmed in an animal model of obese rats, in which EX‑4 was able to improve the function of β‑cells, attenuate oxidative stress, and inhibit the expression levels of TLR4 and NF‑κB p65 subunit in the pancreas of the diet‑induced obese rats. Furthermore, truncation of the TLR4 gene in SD rats delayed the aforementioned damage. In summary, EX‑4 may inhibit lipotoxicity‑induced oxidative stress in β‑cells by inhibiting the activation of the TLR4/NF‑κB signaling pathway.
View Figures
View References

Related Articles

Journal Cover

April-2020
Volume 45 Issue 4

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

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Shen X, Luo L, Yang M, Lin Y, Li J and Yang L: Exendin‑4 inhibits lipotoxicity‑induced oxidative stress in β‑cells by inhibiting the activation of TLR4/NF‑κB signaling pathway. Int J Mol Med 45: 1237-1249, 2020
APA
Shen, X., Luo, L., Yang, M., Lin, Y., Li, J., & Yang, L. (2020). Exendin‑4 inhibits lipotoxicity‑induced oxidative stress in β‑cells by inhibiting the activation of TLR4/NF‑κB signaling pathway. International Journal of Molecular Medicine, 45, 1237-1249. https://doi.org/10.3892/ijmm.2020.4490
MLA
Shen, X., Luo, L., Yang, M., Lin, Y., Li, J., Yang, L."Exendin‑4 inhibits lipotoxicity‑induced oxidative stress in β‑cells by inhibiting the activation of TLR4/NF‑κB signaling pathway". International Journal of Molecular Medicine 45.4 (2020): 1237-1249.
Chicago
Shen, X., Luo, L., Yang, M., Lin, Y., Li, J., Yang, L."Exendin‑4 inhibits lipotoxicity‑induced oxidative stress in β‑cells by inhibiting the activation of TLR4/NF‑κB signaling pathway". International Journal of Molecular Medicine 45, no. 4 (2020): 1237-1249. https://doi.org/10.3892/ijmm.2020.4490