Evidence map›Paper›PMID 29379070›Full record

ArticleScientific reports2018

The transcriptional response to oxidative stress is part of, but not sufficient for, insulin resistance in adipocytes.

Rima Chaudhuri, James R Krycer, Daniel J Fazakerley, Kelsey H Fisher-Wellman, Zhiduan Su, Kyle L Hoehn, Jean Yee Hwa Yang, Zdenka Kuncic, Fatemeh Vafaee, David E James

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.4field-weighted citation impact, top 19% 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

12 citing papers in PubMed, 13 citations in OpenAlex.

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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

10 authors at 4 institutions in 2 countries.

Rima ChaudhuriCharles Perkins Centre, The University of Sydney, Sydney, NSW, 2006, Australia.
James R KrycerCharles Perkins Centre, The University of Sydney, Sydney, NSW, 2006, Australia.
Daniel J FazakerleyCharles Perkins Centre, The University of Sydney, Sydney, NSW, 2006, Australia.ORCID http://orcid.org/0000-0001-8241-2903
Kelsey H Fisher-WellmanDuke Molecular Physiology Institute, Duke University, Durham, NC, 27701, USA.
Zhiduan SuCharles Perkins Centre, The University of Sydney, Sydney, NSW, 2006, Australia.
Kyle L HoehnSchool of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, NSW, 2052, Australia.ORCID http://orcid.org/0000-0002-0214-3238
Jean Yee Hwa YangCharles Perkins Centre, The University of Sydney, Sydney, NSW, 2006, Australia.
Zdenka KuncicCharles Perkins Centre, The University of Sydney, Sydney, NSW, 2006, Australia.ORCID http://orcid.org/0000-0001-6765-3215
Fatemeh VafaeeSchool of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, NSW, 2052, Australia. f.vafaee@unsw.edu.au.ORCID http://orcid.org/0000-0002-7521-2417
David E JamesCharles Perkins Centre, The University of Sydney, Sydney, NSW, 2006, Australia. david.james@sydney.edu.au.
The University of Sydney · AUUNSW Sydney · AUDuke University · USUniversity of Technology Sydney · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Insulin resistance is a major risk factor for metabolic diseases such as Type 2 diabetes. Although the underlying mechanisms of insulin resistance remain elusive, oxidative stress is a unifying driver by which numerous extrinsic signals and cellular stresses trigger insulin resistance. Consequently, we sought to understand the cellular response to oxidative stress and its role in insulin resistance. Using cultured 3T3-L1 adipocytes, we established a model of physiologically-derived oxidative stress by inhibiting the cycling of glutathione and thioredoxin, which induced insulin resistance as measured by impaired insulin-stimulated 2-deoxyglucose uptake. Using time-resolved transcriptomics, we found > 2000 genes differentially-expressed over 24 hours, with specific metabolic and signalling pathways enriched at different times. We explored this coordination using a knowledge-based hierarchical-clustering approach to generate a temporal transcriptional cascade and identify key transcription factors responding to oxidative stress. This response shared many similarities with changes observed in distinct insulin resistance models. However, an anti-oxidant reversed insulin resistance phenotypically but not transcriptionally, implying that the transcriptional response to oxidative stress is insufficient for insulin resistance. This suggests that the primary site by which oxidative stress impairs insulin action occurs post-transcriptionally, warranting a multi-level 'trans-omic' approach when studying time-resolved responses to cellular perturbations.

Indexed as

3T3-L1 CellsAdipocytesAnimalsCell LineDeoxyglucoseDiabetes Mellitus, Type 2GlucoseInsulinInsulin ResistanceMiceOxidative StressSignal TransductionTranscription, GeneticDeoxyglucoseGlucoseInsulin

Identifiers

PMID29379070
PMCPMC5789081
OpenAlexW2805578823

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.