Evidence mapPaperPMID 29040818Full record

ArticleTranslational research : the journal of laboratory and clinical medicine2017

Metformin attenuates ER stress-induced mitochondrial dysfunction.

Qun Chen, Jeremy Thompson, Ying Hu, Anindita Das, Edward J Lesnefsky

Registry-linked trialAbstract read
In one paragraph

Article in Translational research : the journal of laboratory and clinical medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04879511 (Effect of Metformin on Circulating Neuregulin-4 in Children With Type 1 Diabetes), which is not on this map. Cited by 58 papers.

0numbers the graph read from it
0cells of the map it votes in
58citing papers in PubMed
3.5field-weighted citation impact, top 7% 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.

NCT04879511 phase2 / phase3completednot on this mapstarted 2018, after this paper: background citation

Effect of Metformin on Circulating Neuregulin-4 in Children With Type 1 Diabetes

TypeinterventionalSponsorAin Shams UniversityRan2018 to 2021Enrolled80ConditionsEffect of Change in T1DM Glycemic ControlArmsmetformin, Basal/bolus insulin
3 · Its place in the literature

Who cites it

58 citing papers in PubMed, 83 citations in OpenAlex.

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  15. Acute endoplasmic reticulum stress-induced mitochondria respiratory chain damage: The role of activated calpains.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024
    Article
  16. Review
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  18. Endoplasmic reticulum stress and mitochondrial dysfunction during aging: Role of sphingolipids.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2023
    Article
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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

5 authors at 1 institution in 1 country.

Qun ChenDepartment of Medicine, Division of Cardiology, Virginia Commonwealth University, Richmond, Va. Electronic address: qun.chen@vcuhealth.org.
Jeremy ThompsonDepartment of Medicine, Division of Cardiology, Virginia Commonwealth University, Richmond, Va.
Ying HuDepartment of Medicine, Division of Cardiology, Virginia Commonwealth University, Richmond, Va.
Anindita DasDepartment of Medicine, Division of Cardiology, Virginia Commonwealth University, Richmond, Va.
Edward J LesnefskyDepartment of Medicine, Division of Cardiology, Virginia Commonwealth University, Richmond, Va; Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, Va; Department of Physiology and Biophysics, Virginia Commonwealth University, Richmond, Va; McGuire Department of Veterans Affairs Medical Center, Richmond, Va.
Virginia Commonwealth University · US

Funding

Mitochondrial Dysfunction in the Aged Heart: Role of Endoplasmic Reticulum StressI01BX001355 · VA · VA VETERANS ADMINISTRATION HOSPITAL · 2022 to 2025
BLRD VA I01 BX001355NCATS NIH HHS UL1 TR000058NHLBI NIH HHS R01 HL134366NIA NIH HHS R21 AG054975
6 · The paper itself

Abstract

Endoplasmic reticulum (ER) stress, a disturbance of the ER function, contributes to cardiac injury. ER and mitochondria are closely connected organelles within cells. ER stress contributes to mitochondrial dysfunction, which is a key factor to increase cardiac injury. Metformin, a traditional anti-diabetic drug, decreases cardiac injury during ischemia-reperfusion. Metformin also inhibits ER stress in cultured cells. We hypothesized that metformin can attenuate the ER stress-induced mitochondrial dysfunction and subsequent cardiac injury. Thapsigargin (THAP, 3 mg/kg) was used to induce ER stress in C57BL/6 mice. Cell injury and mitochondrial function were evaluated in the mouse heart 48 hours after 1-time THAP treatment. Metformin was dissolved in drinking water (0.5 g/250 ml) and fed to mice for 7 days before THAP injection. Metformin feeding continued after THAP treatment. THAP treatment increased apoptosis in mouse myocardium compared to control. THAP also led to decreased oxidative phosphorylation in heart mitochondria-oxidizing complex I substrates. THAP decreased the calcium retention capacity, indicating that ER stress sensitizes mitochondria to mitochondrial permeability transition pore opening. The cytosolic C/EBP homologous protein (CHOP) content was markedly increased in THAP-treated hearts compared to control, particularly in the nucleus. Metformin prevented the THAP-induced mitochondrial dysfunction and reduced CHOP content in cytosol and nucleus. Thus, metformin reduces cardiac injury during ER stress through the protection of cardiac mitochondria and attenuation of CHOP expression.

Indexed as

AnimalsCalciumCell DeathEndoplasmic Reticulum StressGene Expression RegulationHypoglycemic AgentsMaleMetforminMiceMice, Inbred C57BLMitochondriaThapsigarginTranscription Factor CHOPCalciumDdit3 protein, mouseHypoglycemic AgentsMetforminThapsigarginTranscription Factor CHOP

Identifiers

PMID29040818
PMCPMC5705457
OpenAlexW2757774325

What Socratic holds

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Registered trials

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.