Evidence mapPaperPMID 26158396Full record

ArticleHormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme2016

Tofogliflozin, A Highly Selective Inhibitor of SGLT2 Blocks Proinflammatory and Proapoptotic Effects of Glucose Overload on Proximal Tubular Cells Partly by Suppressing Oxidative Stress Generation.

Y Ishibashi, T Matsui, S Yamagishi

Registry-linked trialAbstract read
PubMed Publisher
In one paragraph

Article in Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04806633 (Dapagliflozin to Prevent the Incidence of Contrast Induced Nephropathy After Heart Catheterization and Percutaneous Coronary Intervention), which is not on this map. Cited by 65 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
65citing papers in PubMed, 1 pooled it
5.3field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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.

NCT04806633 early_phase1unknown statusstarted 2021, after this paper: background citation

Dapagliflozin to Prevent the Incidence of Contrast Induced Nephropathy After Heart Catheterization and Percutaneous Coronary Intervention

Ran2021Enrolled1,722Registered outcomes6Posted comparisons0ConditionsAcute Kidney Injury, Left Cardiac Catheterization, Percutaneous Coronary Intervention, Sodium-glucose Co-transporter 2 InhibitorsArmsDapagliflozin 5mg, Placebo
Open the trial in the graph
3 · Its place in the literature

Who cites it

65 citing papers in PubMed, 1 synthesis or guideline pooled it, 116 citations in OpenAlex.

  1. Pooled it
  2. How do SGLT2 inhibitors protect the kidney? A mediation analysis of the EMPA-REG OUTCOME trial.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2024
    Trial
  3. Trial
  4. Review
  5. Article
  6. Review
  7. Article
  8. Article
  9. Multiple Benefits of Empagliflozin in PCOS: Evidence from a Preclinical Rat Model.Pathophysiology : the official journal of the International Society for Pathophysiology · 2024
    Article
  10. Review
  11. SGLT2 inhibition to target kidney aging.Clinical kidney journal · 2024
    Review
  12. Review
  13. Review
  14. Albuminuria and Serum Tumor Necrosis Factor Receptor Levels in Patients with Type 2 Diabetes on SGLT2 Inhibitors: A Prospective Study.Diabetes therapy : research, treatment and education of diabetes and related disorders · 2024
    Article
  15. Article
  16. Immunomodulatory Effects of SGLT2 Inhibitors-Targeting Inflammation and Oxidative Stress in Aging.International journal of environmental research and public health · 2023
    Review
  17. Article
  18. Review
  19. Review
  20. Review

5 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 1 institution in 1 country.

Y IshibashiDepartment of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Japan.
T MatsuiDepartment of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Japan.
S YamagishiDepartment of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Japan.
Kurume University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Ninety percent of glucose filtered by the glomerulus is reabsorbed by a sodium-glucose cotransporter 2 (SGLT2), which is mainly expressed on S1 and S2 segment of renal proximal tubules. Since SGLT-2-mediated glucose reabsorption is increased under diabetic conditions, selective inhibition of SGLT2 is a potential therapeutic target for the treatment of diabetes. We have recently shown that an inhibitor of SGLT2 has anti-inflammatory and antifibrotic effects on experimental diabetic nephropathy partly by suppressing advanced glycation end products formation and oxidative stress generation in the kidney. However, the direct effects of SGLT2 inhibitor on tubular cell damage remain unclear. In this study, we investigated the effects of tofogliflozin, a highly selective inhibitor of SGLT2 on oxidative stress generation, inflammatory and proapoptotic reactions in cultured human proximal tubular cells exposed to high glucose. Tofogliflozin dose-dependently suppressed glucose entry into tubular cells. High glucose exposure (30 mM) for 4 and 24 h significantly increased oxidative stress generation in tubular cells, which were suppressed by the treatment of tofogliflozin or an antioxidant N-acetylcysteine (NAC). Monocyte chemoattractant protein-1 (MCP-1) gene expression and apoptotic cell death were induced by 4 h- and 8 day-exposure to high glucose, respectively, both of which were also blocked by tofogliflozin or NAC. The present study suggests that SGLT2-mediated glucose entry into tubular cells could stimulate oxidative stress and evoke inflammatory and proapoptotic reactions in this cell type. Blockade of glucose reabsorption in tubular cells by SGLT2 inhibitor might exert beneficial effects on tubulointerstitial damage in diabetic nephropathy.

Indexed as

Sodium-Glucose Transporter 2 InhibitorsApoptosisBenzhydryl CompoundsCell LineChemokine CCL2Gene Expression RegulationGlucoseGlucosidesHumansInflammationKidney Tubules, ProximalOxidative StressReactive Oxygen SpeciesRNA, MessengerSodium-Glucose Transporter 26-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triolBenzhydryl CompoundsChemokine CCL2GlucoseGlucosidesReactive Oxygen SpeciesRNA, MessengerSodium-Glucose Transporter 2Sodium-Glucose Transporter 2 Inhibitors

Identifiers

PMID26158396
OpenAlexW805790533

What Socratic holds

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Read underepoch 390

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 Socratic graph.