AGT and Hyperglycemia: Hyperglycemia activates angiotensin II (Ang II)/AT1R signaling, upregulating TRPC6 expression and inducing pathological calcium influx (intracellular Ca+ concentration > 500 nM), which drives the following pathological effects: Podocyte cytoskeletal disintegration: Calcium-dependent protease calpain cleaves synaptopodin and nephrin, disrupting slit diaphragm integrity; Mitochondrial damage: Calcium overload opens mitochondrial permeability transition pores (mPTP), reducing ATP synthesis by 50–70%.