IRS1 and Hyperglycemia: Meanwhile, chronic metformin treatment further promoted the phosphorylation level of IRS1 mSer1097, a target of mTOR signaling in the liver, in obese model animals 54, which was also augmented in the hippocampus of middle‐aged DIO mice with hyperglycemia compared with that in age‐matched WT mice, regardless of the level of mTOR phosphorylation (Fig. 5A,F,I).