BSL-3 Laboratory (Guangdong), Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou 510515, China.
Guangdong Key Laboratory for Research and Development of Natural Drugs, The Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang 524023, China.
Biochim Biophys Acta Mol Basis Dis. 2022 Oct 1;1868(10):166472. doi: 10.1016/j.bbadis.2022.166472. Epub 2022 Jun 22.
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.
在疫情期间，患有基础疾病的个体通常死亡率更高。糖尿病在全球范围内高发，使其成为登革热患者常见的合并症。因此，了解登革病毒（DENV）感染与糖尿病之间的关系很重要。我们首先证明 DENV-3 感染下调了 IRS-1 的表达。在体外，用 TNF-α 抑制剂和 siRNA 处理 HepG2 细胞证明，在 HepG2 细胞中感染 DENV-3 后，细胞 TNF-α 的分泌增加，这负调控 IRS-1，从而导致胰岛素抵抗状态。在体内，DENV-3 通过促进 TNF-α 的分泌和抑制 IRS-1 的表达，诱导肝细胞胰岛素抵抗（IR）。体内方法还表明，在 DENV-3 感染后，胰岛素抵抗的 C57BL/6 小鼠血清中的 TNF-α 水平增加，而在用 TNF-α 拮抗剂 III 治疗后，感染导致的肝脏 IRS-1 表达上调。此外，转录组分析显示，DENV-3 感染后胰岛素受体信号通路中存在更多负调控事件。这是 DENV-3 感染与胰岛素抵抗之间联系的首次报道，为进一步研究奠定了基础。
