Evidence map›Paper›PMID 33303821›Full record

ArticleScientific reports2020

Saturated fatty acids induce insulin resistance in podocytes through inhibition of IRS1 via activation of both IKKβ and mTORC1.

Benoit Denhez, Marina Rousseau, Crysta Spino, David-Alexandre Dancosst, Marie-Ève Dumas, Andréanne Guay, Farah Lizotte, Pedro Geraldes

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed, 1 pooled it
1.5field-weighted citation impact, top 17% 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

17 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. Article
  5. Article
  6. Review
  7. Review
  8. Article
  9. Review
  10. The mineralocorticoid receptor in diabetic kidney disease.American journal of physiology. Renal physiology · 2024
    Review
  11. Article
  12. Review
  13. Anti-Inflammatory and Anti-Quorum Sensing Effect ofCurrent issues in molecular biology · 2023
    Article
  14. Role of ceramides in diabetic foot ulcers (Review).International journal of molecular medicine · 2023
    Review
  15. Review
  16. Article
  17. 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.

Benoit DenhezFrom the Research Center of the Centre Hospitalier Universitaire de Sherbrooke, Université de Sherbrooke, 3001 12e Ave Nord, Sherbrooke, QC, J1H 5N4, Canada.
Marina RousseauFrom the Research Center of the Centre Hospitalier Universitaire de Sherbrooke, Université de Sherbrooke, 3001 12e Ave Nord, Sherbrooke, QC, J1H 5N4, Canada.
Crysta SpinoFrom the Research Center of the Centre Hospitalier Universitaire de Sherbrooke, Université de Sherbrooke, 3001 12e Ave Nord, Sherbrooke, QC, J1H 5N4, Canada.
David-Alexandre DancosstFrom the Research Center of the Centre Hospitalier Universitaire de Sherbrooke, Université de Sherbrooke, 3001 12e Ave Nord, Sherbrooke, QC, J1H 5N4, Canada.
Marie-Ève DumasFrom the Research Center of the Centre Hospitalier Universitaire de Sherbrooke, Université de Sherbrooke, 3001 12e Ave Nord, Sherbrooke, QC, J1H 5N4, Canada.
Andréanne GuayFrom the Research Center of the Centre Hospitalier Universitaire de Sherbrooke, Université de Sherbrooke, 3001 12e Ave Nord, Sherbrooke, QC, J1H 5N4, Canada.
Farah LizotteFrom the Research Center of the Centre Hospitalier Universitaire de Sherbrooke, Université de Sherbrooke, 3001 12e Ave Nord, Sherbrooke, QC, J1H 5N4, Canada.
Pedro GeraldesFrom the Research Center of the Centre Hospitalier Universitaire de Sherbrooke, Université de Sherbrooke, 3001 12e Ave Nord, Sherbrooke, QC, J1H 5N4, Canada. Pedro.Geraldes@USherbrooke.ca.
Université de Sherbrooke · CACentre Hospitalier Universitaire de Sherbrooke · CA

Funding

CIHR PJT153165
6 · The paper itself

Abstract

Diabetic nephropathy (DN), a microvascular complication of diabetes, is the leading cause of end-stage renal disease worldwide. Multiple studies have shown that podocyte dysfunction is a central event in the progression of the disease. Beside chronic hyperglycemia, dyslipidemia can induce insulin resistance and dysfunction in podocytes. However, the exact mechanisms of free fatty acid (FFA)-induced podocyte insulin unresponsiveness are poorly understood. We used a type 2 diabetic mouse model (db/db) and mouse podocytes exposed to palmitic acid for 24 h followed by an insulin stimulation. Renal function and pathology were evaluated at 25 weeks of age to confirm the DN development. Our results demonstrate that saturated FFA activated the serine/threonine kinases IκB kinase (IKK)β/IκBα and mTORC1/S6K1, but not protein kinase C and c-jun N-terminal kinase, in podocytes and glomeruli of db/db mice. Activation of both kinases promoted serine 307 phosphorylation of IRS1, a residue known to provoke IRS1 inhibition. Using IKK, mTORC1 and ceramide production inhibitors, we were able to blunt IRS1 serine 307 phosphorylation and restore insulin stimulation of Akt. In conclusion, our results indicate that FFA and diabetes contribute to insulin resistance through the activation of IKKβ and S6K1 leading to podocyte dysfunction and DN.

Indexed as

Insulin ResistanceAnimalsDiabetic NephropathiesFatty AcidsI-kappa B KinaseInsulinInsulin Receptor Substrate ProteinsKidneyMechanistic Target of Rapamycin Complex 1MicePhosphorylationPodocytesReceptors, LeptinSerineSignal TransductionFatty AcidsI-kappa B KinaseInsulinInsulin Receptor Substrate ProteinsIrs1 protein, mouseMechanistic Target of Rapamycin Complex 1Receptors, LeptinSerine

Identifiers

PMID33303821
PMCPMC7728775
OpenAlexW3112850846

What Socratic 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 Socratic graph.