ArticleJCI insight2020
Renal protective effects of empagliflozin via inhibition of EMT and aberrant glycolysis in proximal tubules.
Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 138 papers, 2 of them syntheses that pooled it.
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Who cites it
138 citing papers in PubMed, 2 syntheses or guidelines pooled it, 234 citations in OpenAlex.
- The lactate-lactylation axis in renal fibrosis: potential mechanisms in diabetic kidney disease.Annals of medicine · 2025Pooled it
- Key Genetic Components of Fibrosis in Diabetic Nephropathy: An Updated Systematic Review and Meta-Analysis.International journal of molecular sciences · 2022Pooled it
- Bibliometric analysis of SGLT2 inhibitor treatment for diabetic kidney disease.Renal failure · 2026Review
- Cyanoglycosides isolated fromPharmaceutical biology · 2026Article
- Sodium Butyrate Attenuates Renal Fibrosis by Regulating Glycolysis and Histone H4K12 Lactylation in Diabetic Kidney Disease.Diabetes, obesity & metabolism · 2026Article
- Natural products modulate renal metabolic reprogramming in diabetic kidney disease.Journal of translational internal medicine · 2026Article
- Canagliflozin Alleviates Diabetic Glomerular Endothelial Injury via Melibiose in a Microbiota-Dependent Manner.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Overexpression of FTO ameliorates chronic glomerulonephritis by inhibiting glycolysis in glomerular mesangial cells associated with ADPGK mNaunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Metabolic reprogramming in fibrosis-related diseases: underlying mechanisms and therapeutics.Molecular biomedicine · 2026Review
- AARS1 promotes diabetic kidney disease through rewiring Akt and NF-κB signaling to suppress autophagy and sustain inflammation.Cellular & molecular biology letters · 2026Article
- Article
- Next-generation therapeutics for diabetic kidney disease.Nature reviews. Nephrology · 2026Review
- Empagliflozin Ameliorates Diabetic Cardiomyopathy by Inhibiting Ferroptosis via SIRT3: Mechanisms and Therapeutic Implications.Antioxidants (Basel, Switzerland) · 2026Article
- AMPK is dispensable for physiological podocyte and glomerular functions but prevents glomerular fibrosis in experimental diabetes.Cell death discovery · 2026Article
- The biology of PKM2 in the metabolism and senescence in diabetic kidney disease.Journal of diabetes investigation · 2026Review
- Kidney angiopoietin-like protein 4 regulates fibrotic responses in diabetic kidney disease.Frontiers in pharmacology · 2026Review
- Potential Mechanisms of Sodium-Glucose Cotransporter 2 Inhibitors in Regulating Cardiac and Renal Fibrosis.Cardiorenal medicine · 2026Review
- Advances in the Targeted Drug Delivery System for Renal Fibrosis.International journal of nanomedicine · 2026Review
- New Insights into the Role of Mitochondrial Dysfunction in Diabetic Kidney Disease in the Omics Era.Diabetes, metabolic syndrome and obesity : targets and therapy · 2026Review
- Cardiometabolic and renal benefits of sodium-glucose cotransporter 2 inhibitors.Nature reviews. Endocrinology · 2025Review
78 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sodium glucose cotransporter 2 (SGLT2) inhibitors are beneficial in halting diabetic kidney disease; however, the complete mechanisms have not yet been elucidated. The epithelial-mesenchymal transition (EMT) is associated with the suppression of sirtuin 3 (Sirt3) and aberrant glycolysis. Here, we hypothesized that the SGLT2 inhibitor empagliflozin restores normal kidney histology and function in association with the inhibition of aberrant glycolysis in diabetic kidneys. CD-1 mice with streptozotocin-induced diabetes displayed kidney fibrosis that was associated with the EMT at 4 months after diabetes induction. Empagliflozin intervention for 1 month restored all pathological changes; however, adjustment of blood glucose by insulin did not. Empagliflozin normalized the suppressed Sirt3 levels and aberrant glycolysis that was characterized by HIF-1α accumulation, hexokinase 2 induction, and pyruvate kinase isozyme M2 dimer formation in diabetic kidneys. Empagliflozin also suppressed the accumulation of glycolysis byproducts in diabetic kidneys. Another SGLT2 inhibitor, canagliflozin, demonstrated similar in vivo effects. High-glucose media induced the EMT, which was associated with Sirt3 suppression and aberrant glycolysis induction, in the HK2 proximal tubule cell line; SGLT2 knockdown suppressed the EMT, with restoration of all aberrant functions. SGLT2 suppression in tubular cells also inhibited the mesenchymal transition of neighboring endothelial cells. Taken together, SGLT2 inhibitors exhibit renoprotective potential that is partially dependent on the inhibition of glucose reabsorption and subsequent aberrant glycolysis in kidney tubules.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.