IRS1 and type 2 diabetes mellitus: There are some connections between the insulin signaling pathway and this protein, as IR activation phosphorylates and inhibits GSK-3β (199), while in AD, GSK-3β activity is increased as well as in T2DM, and this process enables it to phosphorylate the IR and IRS-1, which decrease the phosphorylation of tyrosine residues of the IR and IRS-1 (200).