Evidence map›Paper›PMID 26698173›Full record

ArticleThe Journal of biological chemistry2016

Sustained Action of Ceramide on the Insulin Signaling Pathway in Muscle Cells: IMPLICATION OF THE DOUBLE-STRANDED RNA-ACTIVATED PROTEIN KINASE.

Rima Hage Hassan, Ana Catarina Pacheco de Sousa, Rana Mahfouz, Isabelle Hainault, Agnieszka Blachnio-Zabielska, Olivier Bourron, Fabien Koskas, Jan Górski, Pascal Ferré, Fabienne Foufelle and 1 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed, 2 pooled it
4.7field-weighted citation impact, top 5% 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

40 citing papers in PubMed, 2 syntheses or guidelines pooled it, 64 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Article
  4. Review
  5. Article
  6. Observational
  7. Review
  8. Review
  9. Review
  10. Review
  11. Review
  12. Review
  13. Article
  14. Article
  15. Review
  16. Positive Effects of Physical Activity on Insulin Signaling.Current issues in molecular biology · 2024
    Review
  17. Review
  18. Circulating Sphingolipids and Glucose Homeostasis: An Update.International journal of molecular sciences · 2023
    Review
  19. Review
  20. Review
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

11 authors at 6 institutions in 2 countries.

Rima Hage HassanFrom INSERM, Unité Mixte de Recherche_S 1138, Centre de Recherche des Cordeliers, 75006 Paris, France, Sorbonne Universités, Université Pierre et Marie Curie Paris 06, Unité Mixte de Recherche_S 1138, Centre de Recherche des Cordeliers, 75006 Paris, France, Université Paris Descartes, Sorbonne Paris Cité, Unité Mixte de Recherche_S 1138, Centre de Recherche des Cordeliers, 75006 Paris, France.
Ana Catarina Pacheco de SousaFrom INSERM, Unité Mixte de Recherche_S 1138, Centre de Recherche des Cordeliers, 75006 Paris, France, Sorbonne Universités, Université Pierre et Marie Curie Paris 06, Unité Mixte de Recherche_S 1138, Centre de Recherche des Cordeliers, 75006 Paris, France, Université Paris Descartes, Sorbonne Paris Cité, Unité Mixte de Recherche_S 1138, Centre de Recherche des Cordeliers, 75006 Paris, France.
Rana MahfouzFrom INSERM, Unité Mixte de Recherche_S 1138, Centre de Recherche des Cordeliers, 75006 Paris, France, Sorbonne Universités, Université Pierre et Marie Curie Paris 06, Unité Mixte de Recherche_S 1138, Centre de Recherche des Cordeliers, 75006 Paris, France, Université Paris Descartes, Sorbonne Paris Cité, Unité Mixte de Recherche_S 1138, Centre de Recherche des Cordeliers, 75006 Paris, France.
Isabelle HainaultFrom INSERM, Unité Mixte de Recherche_S 1138, Centre de Recherche des Cordeliers, 75006 Paris, France, Sorbonne Universités, Université Pierre et Marie Curie Paris 06, Unité Mixte de Recherche_S 1138, Centre de Recherche des Cordeliers, 75006 Paris, France, Université Paris Descartes, Sorbonne Paris Cité, Unité Mixte de Recherche_S 1138, Centre de Recherche des Cordeliers, 75006 Paris, France.
Agnieszka Blachnio-ZabielskaDepartment of Physiology, Medical University of Bialystok, 15-222 Bialystok, Poland, Assistance Publique-Hôpitaux de Paris.
Olivier BourronFrom INSERM, Unité Mixte de Recherche_S 1138, Centre de Recherche des Cordeliers, 75006 Paris, France, Sorbonne Universités, Université Pierre et Marie Curie Paris 06, Unité Mixte de Recherche_S 1138, Centre de Recherche des Cordeliers, 75006 Paris, France, Université Paris Descartes, Sorbonne Paris Cité, Unité Mixte de Recherche_S 1138, Centre de Recherche des Cordeliers, 75006 Paris, France, Département de Diabétologie et Maladies Métaboliques and.
Fabien KoskasService de Chirurgie Vasculaire,Hôpital Pitié-Salpêtrière, 75013 Paris, France.
Jan GórskiDepartment of Physiology, Medical University of Bialystok, 15-222 Bialystok, Poland, Assistance Publique-Hôpitaux de Paris.
Pascal FerréFrom INSERM, Unité Mixte de Recherche_S 1138, Centre de Recherche des Cordeliers, 75006 Paris, France, Sorbonne Universités, Université Pierre et Marie Curie Paris 06, Unité Mixte de Recherche_S 1138, Centre de Recherche des Cordeliers, 75006 Paris, France, Université Paris Descartes, Sorbonne Paris Cité, Unité Mixte de Recherche_S 1138, Centre de Recherche des Cordeliers, 75006 Paris, France.
Fabienne FoufelleFrom INSERM, Unité Mixte de Recherche_S 1138, Centre de Recherche des Cordeliers, 75006 Paris, France, Sorbonne Universités, Université Pierre et Marie Curie Paris 06, Unité Mixte de Recherche_S 1138, Centre de Recherche des Cordeliers, 75006 Paris, France, Université Paris Descartes, Sorbonne Paris Cité, Unité Mixte de Recherche_S 1138, Centre de Recherche des Cordeliers, 75006 Paris, France.
Eric HajduchFrom INSERM, Unité Mixte de Recherche_S 1138, Centre de Recherche des Cordeliers, 75006 Paris, France, Sorbonne Universités, Université Pierre et Marie Curie Paris 06, Unité Mixte de Recherche_S 1138, Centre de Recherche des Cordeliers, 75006 Paris, France, Université Paris Descartes, Sorbonne Paris Cité, Unité Mixte de Recherche_S 1138, Centre de Recherche des Cordeliers, 75006 Paris, France, eric.hajduch@crc.jussieu.fr.
Centre de Recherche des Cordeliers · FRInserm · FRMedical University of Białystok · PLSorbonne Paris Cité · FRUniversité Paris Cité · FRPitié-Salpêtrière Hospital · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

In vivo, ectopic accumulation of fatty acids in muscles leads to alterations in insulin signaling at both the IRS1 and Akt steps. However, in vitro treatments with saturated fatty acids or their derivative ceramide demonstrate an effect only at the Akt step. In this study, we adapted our experimental procedures to mimic the in vivo situation and show that the double-stranded RNA-dependent protein kinase (PKR) is involved in the long-term effects of saturated fatty acids on IRS1. C2C12 or human muscle cells were incubated with palmitate or directly with ceramide for short or long periods, and insulin signaling pathway activity was evaluated. PKR involvement was assessed through pharmacological and genetic studies. Short-term treatments of myotubes with palmitate, a ceramide precursor, or directly with ceramide induce an inhibition of Akt, whereas prolonged periods of treatment show an additive inhibition of insulin signaling through increased IRS1 serine 307 phosphorylation. PKR mRNA, protein, and phosphorylation are increased in insulin-resistant muscles. When PKR activity is reduced (siRNA or a pharmacological inhibitor), serine phosphorylation of IRS1 is reduced, and insulin-induced phosphorylation of Akt is improved. Finally, we show that JNK mediates ceramide-activated PKR inhibitory action on IRS1. Together, in the long term, our results show that ceramide acts at two distinct levels of the insulin signaling pathway (IRS1 and Akt). PKR, which is induced by both inflammation signals and ceramide, could play a major role in the development of insulin resistance in muscle cells.

Indexed as

AnimalsCell LineCeramideseIF-2 KinaseHumansInsulinInsulin Receptor Substrate ProteinsInsulin ResistanceMaleMAP Kinase Kinase 4MiceMuscle, SkeletalPhosphorylationProto-Oncogene Proteins c-aktSignal TransductionCeramideseIF-2 KinaseInsulinInsulin Receptor Substrate ProteinsIRS1 protein, humanIrs1 protein, mouseMAP Kinase Kinase 4protein kinase R, mouseProto-Oncogene Proteins c-aktAkt PKBceramideinsulin signalingprotein kinase RNA-activated (PKR)skeletal muscletype 2 diabetes

Identifiers

PMID26698173
PMCPMC4742763
OpenAlexW2200705322

What OpenQuestion holds

Textmetadata
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.