Evidence map›Paper›PMID 40035128›Full record

ArticleJournal of cachexia, sarcopenia and muscle2025

Deubiquitinating Enzymes Regulate Skeletal Muscle Mitochondrial Quality Control and Insulin Sensitivity in Patients With Type 2 Diabetes.

Wagner S Dantas, Elizabeth C Heintz, Elizabeth R M Zunica, Jacob T Mey, Melissa L Erickson, Kathryn P Belmont, Analisa L Taylor, Gangarao Davuluri, Hisashi Fujioka, Ciarán E Fealy and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of cachexia, sarcopenia and muscle, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
–field-weighted citation impact
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

11 citing papers in PubMed.

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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

13 authors.

Wagner S DantasIntegrated Physiology and Molecular Medicine Laboratory, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, Louisiana, USA.
Elizabeth C HeintzIntegrated Physiology and Molecular Medicine Laboratory, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, Louisiana, USA.
Elizabeth R M ZunicaIntegrated Physiology and Molecular Medicine Laboratory, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, Louisiana, USA.
Jacob T MeyIntegrated Physiology and Molecular Medicine Laboratory, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, Louisiana, USA.
Melissa L EricksonIntegrated Physiology and Molecular Medicine Laboratory, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, Louisiana, USA.
Kathryn P BelmontIntegrated Physiology and Molecular Medicine Laboratory, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, Louisiana, USA.
Analisa L TaylorIntegrated Physiology and Molecular Medicine Laboratory, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, Louisiana, USA.
Gangarao DavuluriIntegrated Physiology and Molecular Medicine Laboratory, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, Louisiana, USA.
Hisashi FujiokaCryo-Electron Microscopy Core, Case Western Reserve University, Cleveland, OH, USA.
Ciarán E FealyLerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USA.
Charles L HoppelIntegrated Physiology and Molecular Medicine Laboratory, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, Louisiana, USA.
Christopher L AxelrodIntegrated Physiology and Molecular Medicine Laboratory, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, Louisiana, USA.
John P KirwanIntegrated Physiology and Molecular Medicine Laboratory, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, Louisiana, USA.ORCID 0000-0001-7321-9917

Funding

Tracking & Evaluation CoreU54GM104940 · NIGMS · LSU PENNINGTON BIOMEDICAL RESEARCH CTR · PI Peter Todd Katzmarzyk · 2012 to 2026
$69.1M
CTSA INFRASTRUCTURE FOR PEDIATRIC RESEARCHUL1RR024989 · NCRR · CASE WESTERN RESERVE UNIVERSITY · PI DAVIS, PAMELA B · 2007 to 2011
$53.7M
Clinical and Translational Science Collaborative of Northern Ohio, Catalyzing Linkages to Equity in Health (CLE Health)UM1TR004528 · NCATS · CASE WESTERN RESERVE UNIVERSITY · PI GRACE A MCCOMSEY · 2023 to 2026
$32.1M
Research BaseP30DK072476 · NIDDK · LSU PENNINGTON BIOMEDICAL RESEARCH CTR · PI ROBERT A KESTERSON · 2005 to 2026
$26.5M
The role of maternal obesity-driven inflammation and adverse pregnancy outcomes in a mouse model of preeclampsiaP20GM135002 · NIGMS · LSU PENNINGTON BIOMEDICAL RESEARCH CTR · PI Jacob T Mey · 2020 to 2026
$18.4M
Transgenics CoreP30GM118430 · NIGMS · LSU PENNINGTON BIOMEDICAL RESEARCH CTR · PI MYNATT, RANDALL LEE · 2016 to 2020
$5.8M
Role and Regulation of Skeletal Muscle Mitochondrial Dynamics in Type 2 DiabetesR01DK108089 · NIDDK · LSU PENNINGTON BIOMEDICAL RESEARCH CTR · PI JOHN P. KIRWAN · 2015 to 2026
$4.9M
The Role of Nuclear Factor Erythroid 2-related factor 2 in Sarcopenic ObesityK99AG083239 · NIA · LSU PENNINGTON BIOMEDICAL RESEARCH CTR · PI DANTAS, WAGNER SILVA · 2024 to 2024
$113k
Cleveland Clinic UL1RR024989NCATS NIH HHS UM1 TR004528NCRR NIH HHS UL1 RR024989NIA NIH HHS K99 AG083239NIA NIH HHS K99AG083239-01NIDDK NIH HHS P30 DK072476NIDDK NIH HHS R01 DK108089NIGMS NIH HHS P20 GM135002NIGMS NIH HHS P30 GM118430NIGMS NIH HHS U54 GM104940NIH HHS P20GM135002NIH HHS P30DK072476NIH HHS P30GM118430
6 · The paper itself

Abstract

backgroundActivation of mitochondrial fission and quality control occur early in the onset of insulin resistance in human skeletal muscle. We hypothesized that differences in mitochondrial dynamics, structure and bioenergetics in humans would explain the onset and progression of type 2 diabetes (T2D).

methodsFifty-eight sedentary adults (37 ± 12 years) were enrolled into one of three groups: (1) healthy weight (HW), (2) overweight and obesity (Ow/Ob), or (3) T2D. Body composition, aerobic capacity, and insulin sensitivity were assessed during a 3-day inpatient stay. A fasted skeletal muscle biopsy was obtained to assess mitochondrial functions. C2C12 myoblasts were transfected with FLAG-HA-USP15 and FLAG-HA-USP30 and harvested to assess mitochondrial dynamics and cellular insulin action.

resultsInsulin sensitivity and aerobic capacity were lower in Ow/Ob (132% and 28%, respectively) and T2D (1024% and 83%, respectively) relative to HW. Patients with T2D presented with elevated skeletal muscle mitochondrial fission (3.2 fold relative to HW and Ow/Ob), decreased fusion, and impairments in quality control. Mitochondrial content was lower in Ow/Ob (26%) and T2D (56%). USP13 (84%), USP15 (96%) and USP30 (53%) expression were increased with decreased Parkin and Ub activation in T2D alone. USP15 (R

conclusionMitochondrial fragmentation bypasses defects in mitophagy to sustain skeletal muscle quality control in patients with T2D.

Indexed as

Diabetes Mellitus, Type 2Insulin ResistanceMitochondria, MuscleMuscle, SkeletalAdultFemaleHumansMaleMiddle AgedMitochondrial Dynamicsbioenergeticsfissionfusionmitochondriaobesityquality controltype 2 diabetes

Identifiers

PMID40035128
PMCPMC11876994

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Registered trials

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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.