Di-n-butyl phthalate regulates insulin sensitivity in human skeletal muscle cell line through the PI3K-AKT-GLUT4 signaling pathway

Abstract

Abstract Background Dibutyl phthalate (DBP) exposure is a serious environmental problem causing human health threats in China and is closely related to the development of insulin resistance, but its mechanism is unclear. Skeletal muscle tissue is one of the important tissues involved in insulin resistance, and its molecular mechanisms may involve various links of the insulin signaling cascade in muscle cells. Methods In this study, the mRNA and protein expression of the above signaling gene were detected and quantified by Real-time quantitative PCR (RT-qPCR) and Western blotting in human skeletal muscle cell line HSkMC cells, and the InsR-IRS1-PI3K-AKT-GLUT4 signaling pathway as the entry point. Results The mRNA levels of InsR, IRS-1, PI3K, AKT2, and GLUT4 were reduced after DBP treatment compared with control cells.DBP and PI3K inhibitor BKMl20 or DBP transfected with PTEN overexpression lentivirus further reduced the mRNA expression levels of PI3K, AKT2, and GLUT4. In addition, DBP treatment also reduced the expression of InsR, IRS-1, PI3K, AKT2, and GLUT4 and the phosphorylation of AKT2, but both DBP with BKMl20 or DBP was transfected with PTEN overexpression. Conclusions Based on the above results, this study is the first to find a possible molecular mechanism of DBP in skeletal muscle insulin resistance through regulating the PI3K-dependent insulin signaling pathway of skeletal muscle cells, providing a rationale for the pathophysiological changes in the initiation and progression of insulin resistance caused by DBP.