IRS1 and Insulin resistance: In vitro studies using cellular models of human insulin resistance demonstrated that decreased expression of SHBG protein and mRNA levels, along with decreased mRNA and protein levels of IRS-1, IRS-2, PI3Kp85a and GLUT-3 and GLUT-4, indicate that SHBG may down-regulate the PI3K/AKT pathway involved in the development of local and systemic insulin resistance [41].