Data from: SGLT2 inhibition attenuates renal tubular senescence by suppressing CTRP1-mediated glucotoxic stress in diabetic kidney disease

Bioinformatic analysis of CTRP1-deficient mice revealed consistent SGLT2 downregulation, which was validated experimentally in NRK-52E cells, where CTRP1 overexpression increased SGLT2 expression and glucose uptake, particularly under hyperglycemic conditions. In HFD/STZ/UNx-induced DKD rats, dapagliflozin (0.1 mg/kg/day) improved metabolic abnormalities and renal dysfunction and attenuated tubular senescence. Dapagliflozin suppressed CTRP1–SGLT2 axis activation, reduced glucose uptake in renal tubular cells, and markedly decreased the proportion of CTRP1⁺SGLT2⁺ double-positive tubular cells.

These findings support the presence of a previously unrecognized CTRP1–SGLT2 signaling axis associated with glucose-mediated tubular senescence in DKD and provide mechanistic insight into SGLT2 inhibitor-mediated renoprotection.