TNF-α promotes insulin resistance in obstructive sleep apnea-hypopnea syndrome.

Abstract

Obstructive sleep apnea hypopnea syndrome (OSAHS) is the most serious among children with sleep disordered breathing. The present study aimed to investigate whether TNF-α could decrease the glucose transporter type 4 insulin-responsive (GLUT-4) expression to promote insulin resistance through the TNF-α/IKKβ/IKβ/NF-κB signaling pathway in OSAHS. In total, 30 obese children with OSAHS and 30 non-OSAHS obese children were enrolled into the present study. TNF-α expression in adenoid tissues was detected by western blot analysis and immunohistochemistry. The expression of inflammatory factors (IL-1β, IL-6 and IFN-γ) and TNF-α/IKKβ/IKβ/NF-κB signaling pathway-associated proteins was also detected by western blot analysis. The expression of insulin resistance-associated factors, insulin receptor substrate 1 (IRS1) and GLUT4, was determined by western blot analysis and immunohistochemistry. TNF-α expression was increased in adenoid tissues of children with OSAHS, which was also confirmed by immunohistochemistry. The expression levels of IL-1β, IL-6 and IFN-γ were all upregulated in adenoid tissues of children with OSAHS. The expression of IRS1 and GLUT4 was decreased in adenoid tissues of obese children with OSAHS and the result of immunohistochemistry was consistent with the result of western blot analysis. The protein level of TNF-α, and ratio of phosphorylated (p-)/total (t)-IKKβ, p/t-IKβ and p/t-NF-κB was increased in adenoid tissues of children with OSAHS. TNF-α could suppress the GLUT4 expression to promote insulin resistance by TNF-α/IKKβ/IKβ/NF-κB signaling pathway in OSAHS.