Dapagliflozin alleviates advanced glycation end product induced podocyte injury through AMPK/mTOR mediated autophagy pathway

Excessive accumulation of advanced glycation end products (AGEs) contributes to autophagy interruption on podocytes and insufficient autophagy on podocytes is accountable to podocyte injury and eventually accelerates the advancement of DN. SGLT2 inhibitors have been confirmed excellent renoprotection in DN whereas the mechanism for such benefit is not fully illustrated. Here, we report dapagliflozin, an SGLT2 inhibitor, ameliorated the pro-inflammatory cytokines release and apoptosis level concomitant with increasing Synaptopodin level on AGE-induced podocytes. Furthermore, dapagliflozin manifested autophagy promotion on AGE-induced podocytes as evident by the upregulated Beclin and LC3II/LC3I ratio levels attendant with the shrunk p62 level. However, The protective effect of dapagliflozin was blunted by 3-MA, an autophagy inhibitor. Additionally, the effect of dapagliflozin on autophagy was relevant to the regulation of the AMPK-mTOR signal pathway. Taken together, dapagliflozin effectively mitigated AGE-induced podocyte injury through AMPK-mTOR mediated upregulation of autophagy. It may offer a novel mechanism to further elucidate the renoprotective effect on SGLT2 inhibitors.