Metformin protects podocytes by inhibiting the MAPK14–SLC7A11–GPX4 axis and dysregulation of fatty acid metabolism
Authors' conclusion
Our study reveals podocyte ferroptosis to be a central pathogenic event in human diabetic nephropathy, repositioning metformin as a direct ferroptosis inhibitor that preserves podocyte integrity via the MAPK14-SLC7A11-GPX4 axis.
Study context
- Population
- Individuals with diabetic nephropathy and healthy control individuals; db/db mouse models of diabetic nephropathy; in vitro podocytes156,043 kidney nuclei
- Comparison
- Diabetic nephropathy vs healthy controls; metformin in murine models and in vitro
- Outcome
- Podocyte pathways and metformin effects
Methodological detailsintegrative multi-omics, single-nucleus RNA-seq (snRNA-seq), db/db mouse models, spatial metabolomics, in vitro podocyte cultures, targeted urinary metabolomics
- Integrative multi-omics
- snRNA-seq
- Db/db mouse models
- Spatial metabolomics
- In vitro podocyte cultures
- Targeted urinary metabolomics
Main finding
As reported in the abstract
Urinary palmitoylcarnitine as key biomarker of a urinary fatty acid signature, AUC
0.974
Original publication
Metformin protects podocytes by inhibiting the MAPK14–SLC7A11–GPX4 axis and dysregulation of fatty acid metabolism. Diabetologia. Published 3 August 2026. doi:10.
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