IRS1 and Insulin resistance: Consistent with such findings, SOCS3 overexpression decreases the tyrosine phosphorylation levels of IRS1 and inhibits the activity of phosphatidylinositol-3 kinase (PI3K), a downstream signaling element of IRS1 (Ueki et al., 2004a; Yang et al., 2012), revealing a pivotal role of SOCS3 in insulin resistance.