Evidence map›Paper›PMID 31963528›Full record

ArticleMolecules (Basel, Switzerland)2020

PPARα-Dependent Modulation by Metformin of the Expression of OCT-2 and MATE-1 in the Kidney of Mice.

Adriano Cleis Arruda, Mauro Sérgio Perilhão, Warley Almeida Santos, Marcos Fernandes Gregnani, Alexandre Budu, José Cesar Rosa Neto, Gabriel Rufino Estrela, Ronaldo Carvalho Araujo

Open access · goldAbstract read
In one paragraph

Article in Molecules (Basel, Switzerland), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
0.9field-weighted citation impact, top 24% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 15 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Peroxisome Proliferator-Activated Receptor-α (International journal of molecular sciences · 2022
    Article
  8. Review
  9. Pharmaceutics · 2021
    Article
  10. Article
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

8 authors at 2 institutions in 1 country.

Adriano Cleis ArrudaDepartment of Biophysics, Federal University of São Paulo, 04039032 São Paulo, Brazil.
Mauro Sérgio PerilhãoDepartment of Biophysics, Federal University of São Paulo, 04039032 São Paulo, Brazil.
Warley Almeida SantosDepartment of Biophysics, Federal University of São Paulo, 04039032 São Paulo, Brazil.
Marcos Fernandes GregnaniDepartment of Biophysics, Federal University of São Paulo, 04039032 São Paulo, Brazil.
Alexandre BuduDepartment of Biophysics, Federal University of São Paulo, 04039032 São Paulo, Brazil.
José Cesar Rosa NetoDepartment Cell Biology and Development, Institute of Biomedical Sciences, University of São Paulo, 05508000 São Paulo, Brazil.ORCID 0000-0001-7019-9762
Gabriel Rufino EstrelaDepartment of Clinical and Experimental Oncology, Discipline of Hematology and Haematotherapy, Federal University of São Paulo, 04037002 São Paulo, Brazil.ORCID 0000-0003-2858-5111
Ronaldo Carvalho AraujoDepartment of Biophysics, Federal University of São Paulo, 04039032 São Paulo, Brazil.
Universidade Federal de São Paulo · BRUniversidade de São Paulo · BR

Funding

Fundação de Amparo à Pesquisa do Estado de São Paulo 2015/20082-7
6 · The paper itself

Abstract

Metformin is the first-line drug for type 2 diabetes mellitus control. It is established that this drug traffics through OCT-2 and MATE-1 transporters in kidney tubular cells and is excreted in its unaltered form in the urine. Hereby, we provide evidence that points towards the metformin-dependent upregulation of OCT-2 and MATE-1 in the kidney via the transcription factor proliferator-activated receptor alpha (PPARα). Treatment of wild type mice with metformin led to the upregulation of the expression of OCT-2 and MATE-1 by 34% and 157%, respectively. An analysis in a kidney tubular cell line revealed that metformin upregulated PPARα and OCT-2 expression by 37% and 299% respectively. MK-886, a PPARα antagonist, abrogated the OCT-2 upregulation by metformin and reduced MATE-1 expression. Conversely, gemfibrozil, an agonist of PPARα, elicited the increase of PPARα, OCT-2, and MATE-1 expression by 115%, 144%, and 376%, respectively. PPARα knockout mice failed to upregulate both the expression of OCT-2 and MATE-1 in the kidney upon metformin treatment, supporting the PPARα-dependent metformin upregulation of the transporters in this organ. Taken together, our data sheds light on the metformin-induced mechanism of transporter modulation in the kidney, via PPARα, and this effect may have implications for drug safety and efficacy.

Indexed as

AnimalsCell LineChlorobenzenesGemfibrozilGene Expression RegulationGene Knockout TechniquesIndolesKidneyMaleMetforminMiceOrganic Cation Transporter 2Organic Cation Transport ProteinsPPAR alphaUp-RegulationChlorobenzenesGemfibrozilIndolesMATE1 protein, mouseMetforminMK-886Organic Cation Transporter 2Organic Cation Transport ProteinsPPAR alphaPpara protein, mouseSlc22a2 protein, mousekidneyMATE-1metforminOCT-2PPARαtranscription

Identifiers

PMID31963528
PMCPMC7024194
OpenAlexW3000406002

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.