While an age-related increase in the phosphorylation of IRS1 at mSer612 and mSer632/635 accompanied by sustained phosphorylation of IRS1 at T2DM-related mSer1097 site and of AMPK was observed in the hippocampi of middle-aged APPKINL-G-F mice showing memory decline (Figure 5E, Figure S4I, Table S1), there were no significant differences in phosphorylation levels at mSer307 site and of p70S6K between middle-aged WT and APPKINL-G-F mice (Figure 5E,F) owing to the age-related elevation of these factors (Figure 3D,E). This evidence concerns the gene RPS6KB1 and type 2 diabetes mellitus.