Taken together, these results suggest that the reciprocal effects of the phosphorylation of IRS1 at T2DM- or age-related Ser sites and downstream components via feedback loops that may lead to the common alterations in the activity of p70S6K and AMPK are involved in Aβ-unrelated memory decline; however, the modification of IRS1 through Ser sites is not required for the onset of memory deficits in STZ-induced T1DM mice. The gene discussed is RPS6KB1; the disease is type 1 diabetes mellitus.