Evidence map›Paper›PMID 30874600›Full record

ArticleScientific reports2019

Iron induces insulin resistance in cardiomyocytes via regulation of oxidative stress.

Hye Kyoung Sung, Erfei Song, James Won Suk Jahng, Kostas Pantopoulos, Gary Sweeney

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
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.

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

41 citing papers in PubMed, 69 citations in OpenAlex.

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  6. Hydrogen Sulfide (HAntioxidants (Basel, Switzerland) · 2025
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 1 country.

Hye Kyoung SungDepartment of Biology, York University, Toronto, Ontario, Canada.
Erfei SongDepartment of Biology, York University, Toronto, Ontario, Canada.ORCID 0000-0002-2492-5820
James Won Suk JahngDepartment of Biology, York University, Toronto, Ontario, Canada.
Kostas PantopoulosLady Davis Institute for Medical Research and McGill University, Montreal, Quebec, Canada.ORCID 0000-0002-2305-0057
Gary SweeneyDepartment of Biology, York University, Toronto, Ontario, Canada. gsweeney@yorku.ca.
York University · CAMcGill University · CA

Funding

CIHR
6 · The paper itself

Abstract

Iron overload is associated with various pathological changes which contribute to heart failure. Here, we examined mechanisms via which iron alters cardiomyocyte insulin sensitivity. Treatment of primary adult and neonatal cardiomyocytes as well as H9c2 cells with iron decreased insulin sensitivity determined via Western blotting or immunofluorescent detection of Akt and p70S6K phosphorylation and glucose uptake. Using CellROX deep red or DCF-DA probes we also observed that iron increased generation of reactive oxygen species (ROS), and that pretreatment with the superoxide dismutase mimetic MnTBAP reduced ROS production and attenuated iron-induced insulin resistance. SKQ1 and allopurinol but not apocynin reduced iron-induced ROS suggesting mitochondria and xanthine oxidase contribute to cellular ROS in response to iron. Western blotting for LC3-I, LC3-II and P62 levels as well as immunofluorescent co-detection of autophagosomes with Cyto-ID and lysosomal cathepsin activity indicated that iron attenuated autophagic flux without altering total expression of Atg7 or beclin-1 and phosphorylation of mTORC1 and ULK1. This conclusion was reinforced via protein accumulation detected using Click-iT HPG labelling after iron treatment. The adiponectin receptor agonist AdipoRon increased autophagic flux and improved insulin sensitivity both alone and in the presence of iron. We created an autophagy-deficient cell model by overexpressing a dominant-negative Atg5 mutant in H9c2 cells and this confirmed that reduced autophagy flux correlated with less insulin sensitivity. In conclusion, our study showed that iron promoted a cascade of ROS production, reduced autophagy and insulin resistance in cardiomyocytes.

Indexed as

AnimalsAutophagosomesAutophagyAutophagy-Related Protein 5Beclin-1Cell LineInsulin ResistanceIronLysosomesMitochondriaMyoblasts, CardiacMyocytes, CardiacOxidative StressRatsReactive Oxygen SpeciesSuperoxide DismutaseAutophagy-Related Protein 5Beclin-1IronReactive Oxygen SpeciesSuperoxide Dismutase

Identifiers

PMID30874600
PMCPMC6420583
OpenAlexW2922255565

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.