SGLT2 inhibition attenuates diabetic tubulopathy by suppressing SGK1-mediated pyroptosis.

ABSTRACT:

Background

Diabetic tubulopathy is increasingly recognized as a pivotal contributor to diabetic kidney disease (DKD) progression. Excessive pyroptosis of renal tubular epithelial cells exacerbates inflammation and tissue injury. Although sodium-glucose cotransporter 2 (SGLT2) inhibitors confer renal protection, their mechanistic linkage to pyroptosis remains unclear.

Methods

Renal biopsies from DKD patients, STZ-induced diabetic mice, and high glucose (HG)-stimulated HK-2 cells were analyzed. Pyroptosis markers and SGK1 signaling were assessed following SGLT2 knockdown, overexpression, or treatment with SGLT2 inhibitor empagliflozin (EMPA) and the SGK1 inhibitor EMD638683 (EMD).

Results

SGLT2 and Gasdermin D N-terminal domain (GSDMD-N) were upregulated in DKD kidneys

SUBMITTER: Shi X 

PROVIDER: S-EPMC12476994 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature