SMAD3 and type 2 diabetes mellitus: In addition, our data suggest that amelioration of cardiac fibrosis with metformin—via the inhibition of iNOS/mTOR/TIMP-1 cell signaling—mirrors the results of other studies in which metformin inhibited cardiac fibrosis, the latter being induced by either pressure overload [38] or T2DM [20] via the inhibition of TGFβ1/Smad3 and ROS/p53 cell signaling, respectively.