AGT and Hyperglycemia: In the diabetic kidney, various stimuli such as hyperglycemia, reactive oxygen species (ROS), angiotensin II (Ang II), thrombospondin-1 (TSP-1), and advanced glycation end products (AGEs) induce TGF-β1 synthesis and activate TGF-β1-dependent signaling, which results in diverse injurious changes underlying DN.