2. Academic Validation
  3. Dengue virus is involved in insulin resistance via the downregulation of IRS-1 by inducing TNF-α secretion

Dengue virus is involved in insulin resistance via the downregulation of IRS-1 by inducing TNF-α secretion

  • Biochim Biophys Acta Mol Basis Dis. 2022 Oct 1;1868(10):166472. doi: 10.1016/j.bbadis.2022.166472.
Xuling Liu 1,  Zuxin Liang 1,  Hongwei Duan 1,  Jianhai Yu 1,  Zhiran Qin 1,  Jingshu Li 1,  Li Zhu 1,  Qinghua Wu 1,  Weiwei Xiao 1,  Chenguang Shen 1,  Chengsong Wan 1,  Kefeng Wu 2,  Hua Ye 3,  Bao Zhang 4,  Wei Zhao 5
Affiliations

Affiliations

  • 1 BSL-3 Laboratory (Guangdong), Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou 510515, China.
  • 2 Guangdong Key Laboratory for Research and Development of Natural Drugs, The Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang 524023, China.
  • 3 Guangdong Key Laboratory for Research and Development of Natural Drugs, The Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang 524023, China. Electronic address: yehua2008@foxmail.com.
  • 4 BSL-3 Laboratory (Guangdong), Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou 510515, China. Electronic address: zhangb@smu.edu.cn.
  • 5 BSL-3 Laboratory (Guangdong), Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou 510515, China. Electronic address: zhaowei@smu.edu.cn.
PMID: 35752384 DOI: 10.1016/j.bbadis.2022.166472
Abstract

During the epidemic, the individuals with underlying diseases usually have a higher rate of mortality. Diabetes is highly prevalent worldwide, making it a frequent comorbidity in dengue fever patients. Therefore, understanding the relationship between Dengue virus (DENV) Infection and diabetes is important. We first demonstrated that DENV-3 Infection down-regulated the expression of IRS-1. In vitro, treatment of HepG2 cells with TNF-α inhibitors and siRNA proved that after DENV-3 Infection in HepG2 cells, cellular TNF-α secretion was increased, which negatively regulated IRS-1, thereby leading to an insulin-resistant state. In vivo, DENV-3 induced Insulin resistance (IR) in hepatocytes by promoting the secretion of TNF-α and inhibiting the expression of IRS-1 was proved. In vivo approaches also showed that after DENV-3 Infection, TNF-α levels in the serum of C57BL/6 mice with Insulin resistance increased, and upon TNF-α antagonist III treatment, IRS-1 expression in the liver, reduced by Infection, was upregulated. In addition, transcriptomic analysis revealed more negative regulatory events in the Insulin Receptor signaling pathway after DENV-3 Infection. This is the first report of a link between DENV-3 Infection and Insulin resistance, and it lays a foundation for further research.

Keywords

Dengue virus; IRS-1; Insulin resistance; TNF-α.

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