The coupling of PI3K/Akt to IGF-1 and IR can be eliminated through serine phosphorylation of insulin receptor substrate-1 (IRS-1), mediated by mTOR, and IRS-1 inactivation and degradation, which is a prominent trigger of brain insulin resistance (BIR) (Tanti and Jager, 2009). This evidence concerns the gene IRS1 and Insulin resistance.