Inhibition of TLR4 protects rat islets against lipopolysaccharide-induced dysfunction

  • Authors:
    • Xiao Wang
    • Qin Min Ge
    • Fan Bian
    • Yan Dong
    • Chun Mei Huang
  • View Affiliations

  • Published online on: December 30, 2016     https://doi.org/10.3892/mmr.2016.6097
  • Pages: 805-812
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Abstract

Oxidative stress leads to dysfunction in pancreatic cells, causing a reduction in insulin secretion following exposure to glucose. Toll-like receptor 4 (TLR4) may be activated by exposure to lipopolysaccharide (LPS) stress. TLR4 may mediate the initiation of inflammatory and immune defense responses; however, the importance of the LPS/TLR4 interaction in apoptosis induced by oxidative stress in pancreatic β cells remains to be elucidated. The present study aimed to investigate the importance of TLR4 during LPS‑induced oxidative stress, apoptosis and dysfunction of insulin secretion in isolated islets of rats. LPS‑induced stimulation of TLR4 increased the production of reactive oxygen species and promoted apoptosis by upregulating the expression levels of caspase‑3, poly ADP ribose polymerase and altering the expression ratio of B‑cell lymphoma‑2 (Bcl‑2)/Bcl‑2 associated X protein. Additionally, the insulin secretion of islets cells was reduced. Anti‑TLR4 antibody and a knockdown of TLR4 by TLR4‑short hairpin RNA were used to inhibit TLR4 activity, which may reverse LPS‑induced events. The present study determined that in islets exposed to LPS oxidative stress, dysfunction may be partly mediated via the TLR4 pathway. Inhibition of TLR4 may prevent dysfunction of rat islets due to oxidative stress. The present study revealed that targeting the LPS/TLR4 signaling pathway and antioxidant therapy may be a novel treatment for the severely septic patients with hyperglycemia stress.
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February-2017
Volume 15 Issue 2

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Wang X, Ge QM, Bian F, Dong Y and Huang CM: Inhibition of TLR4 protects rat islets against lipopolysaccharide-induced dysfunction. Mol Med Rep 15: 805-812, 2017
APA
Wang, X., Ge, Q.M., Bian, F., Dong, Y., & Huang, C.M. (2017). Inhibition of TLR4 protects rat islets against lipopolysaccharide-induced dysfunction. Molecular Medicine Reports, 15, 805-812. https://doi.org/10.3892/mmr.2016.6097
MLA
Wang, X., Ge, Q. M., Bian, F., Dong, Y., Huang, C. M."Inhibition of TLR4 protects rat islets against lipopolysaccharide-induced dysfunction". Molecular Medicine Reports 15.2 (2017): 805-812.
Chicago
Wang, X., Ge, Q. M., Bian, F., Dong, Y., Huang, C. M."Inhibition of TLR4 protects rat islets against lipopolysaccharide-induced dysfunction". Molecular Medicine Reports 15, no. 2 (2017): 805-812. https://doi.org/10.3892/mmr.2016.6097