O-GlcNAc modification of IRS-1 and AKT inhibits their activity either by disruption of their interaction with PI3K and PDK1 kinases, respectively, in 3T3-L1 adipocytes and MCF-7 breast cancer cell lines (17, 26), either by a “Yin-Yang” competition mechanism with activating phosphorylation as described in rat primary adipocytes and INS-1 pancreatic β cell lines (25, 27). This evidence concerns the gene AKT1 and breast cancer.