ArticleCells2021
Dapagliflozin Restores Impaired Autophagy and Suppresses Inflammation in High Glucose-Treated HK-2 Cells.
Article in Cells, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
67 citing papers in PubMed, 1 synthesis or guideline pooled it, 107 citations in OpenAlex.
- Refractory IgA Nephropathy: A Challenge for Future Nephrologists.Medicina (Kaunas, Lithuania) · 2024Pooled it
- Inflammation as a therapeutic target to improve kidney and cardiovascular outcomes.Nature reviews. Nephrology · 2026Review
- Dapagliflozin Beyond Glucose Lowering: Mechanisms of Renal and Systemic Protection.Pathophysiology : the official journal of the International Society for Pathophysiology · 2026Review
- Autophagy and Mitophagy in Hypertensive Chronic Kidney Disease: Evidence Grading, Cell-Type Divergence, and a Working Lysosomal Hypothesis.Life (Basel, Switzerland) · 2026Review
- Selective autophagy in kidney health and disease.Nature reviews. Nephrology · 2026Review
- SGLT2 Inhibitors in Alzheimer's Disease: Biochemical Insights and Therapeutic Potential.International journal of molecular sciences · 2026Review
- Dapagliflozin attenuates cisplatin-induced nephrotoxicity in rats through modulation of ROS/NF-κB, BCL2/Bax and PINK1/Parkin signaling pathways.Scientific reports · 2026Article
- Article
- Glucagon-Like Peptide-1 Receptor Agonists in Chronic Kidney Disease: Mechanisms and Clinical Perspectives.Kidney medicine · 2026Review
- Dapagliflozin regulates chondrocyte homeostasis and protects against osteoarthritis via targets AMPKα and SGLT2.Cell death discovery · 2026Article
- Perillaldehyde inhibits oxidative stress, NLRP3-mediated inflammation and fibrosis in diabetic nephropathy through regulating HMOX1.Hereditas · 2026Article
- γ-Oryzanol Ameliorates Endothelial Replicative Senescence via Downregulation of SGLT2 Expression to Attenuate NADPH-Driven Oxidative Stress.Biomolecules & therapeutics · 2026Article
- Emerging therapeutic pipelines on kidney fibrosis: challenges in translational research.Journal of translational medicine · 2026Review
- Progranulin Deficiency Improves Metabolic Stress Yet Falls Short of Sodium-Glucose Cotransporter-2 Inhibition in Autophagy-Linked Renal Protection.Endocrinology and metabolism (Seoul, Korea) · 2026Article
- Tubular injury in diabetic kidney disease: a focus on regulated cell death.Frontiers in endocrinology · 2026Review
- Empagliflozin and memantine combination ameliorates cognitive impairment in scopolamine + heavy metal mixture-induced Alzheimer's disease in rats: role of AMPK/mTOR, BDNF, BACE-1, neuroinflammation, and oxidative stress.Inflammopharmacology · 2025Article
- Impact of sodium-glucose transport protein-2 (SGLT2) inhibitors on the inflammasome pathway in acute myocardial infarction in type 2 diabetes mellitus: a comprehensive review.Cardiovascular diabetology · 2025Review
- Targeting senescence to prevent diabetic kidney disease: Exploring molecular mechanisms and potential therapeutic targets for disease management.Diabetic medicine : a journal of the British Diabetic Association · 2025Review
- Dapagliflozin ameliorates Lafora disease phenotype in a zebrafish model.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2025Article
- Exploring the disconnect: mechanisms underpinning the absence of physical function improvement with SGLT2 inhibitors.Frontiers in systems biology · 2025Article
7 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
5 authors at 1 institution in 1 country.
Funding
Abstract
Sodium-glucose cotransporter2 (SGLT2) inhibitors have a reno-protective effect in diabetic kidney disease. However, the detailed mechanism remains unclear. In this study, human proximal tubular cells (HK-2) were cultured in 5 mM glucose and 25 mM mannitol (control), 30 mM glucose (high glucose: HG), or HG and SGLT2 inhibitor, dapagliflozin-containing medium for 48 h. The autophagic flux was decreased, accompanied by the increased phosphorylation of S6 kinase ribosomal protein (p-S6RP) and the reduced phosphorylation of AMP-activated kinase (p-AMPK) expression in a HG condition. Compared to those of the control, dapagliflozin and SGLT2 knockdown ameliorated the HG-induced alterations of p-S6RP, p-AMPK, and autophagic flux. In addition, HG increased the nuclear translocation of nuclear factor-κB p65 (NF-κB) p65 and the cytoplasmic nucleotide-binding oligomerization domain-like receptor 3 (NLRP3), mature interleukin-1β (IL-1β), IL-6, and tumor necrosis factorα (TNFα) expression. Dapagliflozin, SGLT2 knockdown, and NF-κB p65 knockdown reduced the extent of these HG-induced inflammatory alterations. The inhibitory effect of dapagliflozin on the increase in the HG-induced nuclear translocation of NF-κB p65 was abrogated by knocking down AMPK. These data indicated that in diabetic renal proximal tubular cells, dapagliflozin ameliorates: (1) HG-induced autophagic flux reduction, via increased AMPK activity and mTOR suppression; and (2) inflammatory alterations due to NF-κB pathway suppression.
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Registered trials
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.