SHBG expression is correlated with PI3K/AKT pathway activity in a cellular model of human insulin resistance

Abstract

Decreased sex hormone-binding globulin (SHBG) expression is an independent risk factor for gestational diabetes mellitus(GDM).However, the mechanisms that link low SHBG expression and insulin resistance in GDM is unclear. In this study, we investigated the placenta SHBG in the PI3K/AKT pathway to reveal the mechanism that links decreased SHBG to insulin resistance. A insulin resistance cells model was established by the method of insulin stimulation. Two groups were set up, HTR8/Svneo cells and insulin-resistance cells of HTR8/SVneo. The expression of SHBG and PI3K/AKT associated factors were detected using real-time PCR and western blotting and their correlations were analyzed. The results showed that SHBG protein and mRNA levels in insulin resistance cells were both significantly lower. Along with decreased SHBG expression, the mRNA and protein levels of IRS-1, IRS-2, PI3Kp85α and GLUT-3, GLUT-4 decreased significantly. However, the expression of GLUT-1 increased significantly. Pearson correlation analysis showed that SHBG mRNA expression was positively correlated with IRS-1, IRS-2 and PI3Kp85α mRNA levels. According to the results, low SHBG expression not only participates in the development of local insulin resistance, but may also play an important role in PI3K/AKT pathway-mediated systemic insulin resistance and gestational diabetes.