IRS1 and Insulin resistance: Decrease insulin resistance and increased insulin sensitivity are the main mechanisms underlying the therapeutic effects of metformin (Giannarelli et al., 2003), so we examined changes in the insulin signaling pathway components insulin receptor substrates 1 and 2 (IRS1 and IRS2), Akt, and GSK-3β among adult WT mice and T2DM mice intraperitoneally pretreated with metformin 50 mg/kg or vehicle 1 h before long-term isoflurane or control inhalation.