IRS1 and type 2 diabetes mellitus: Among these S/T kinases, GSK3β is especially important for insulin sensitivity of skeletal muscle.12 GSK3β is constitutively active and can be deactivated by insulin-stimulated Akt.13 In T2D patients, impaired insulin signaling diminishes Akt-mediated suppression of GSK3β and subsequently enhances the inhibitory phosphorylation of IRS1, thereby exacerbating insulin resistance.