Evidence map›Paper›PMID 26668395›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2015

Musclin is an activity-stimulated myokine that enhances physical endurance.

Ekaterina Subbotina, Ana Sierra, Zhiyong Zhu, Zhan Gao, Siva Rama Krishna Koganti, Santiago Reyes, Elizabeth Stepniak, Susan A Walsh, Michael R Acevedo, Carmen M Perez-Terzic and 2 more

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 122 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
122citing papers in PubMed, 1 pooled it
5.9field-weighted citation impact, top 3% 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

122 citing papers in PubMed, 1 synthesis or guideline pooled it, 183 citations in OpenAlex.

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  6. Myokines and mitochondrial function in cardiometabolic diseases.Journal of physiology and biochemistry · 2026
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62 more citing papers are in PubMed but not listed here.

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

12 authors at 3 institutions in 1 country.

Ekaterina SubbotinaDepartment of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52242;
Ana SierraDepartment of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52242;
Zhiyong ZhuDepartment of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52242;
Zhan GaoDepartment of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52242;
Siva Rama Krishna KogantiDepartment of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52242;
Santiago ReyesDepartment of Internal Medicine, Mayo Clinic, Rochester, MN 55905;
Elizabeth StepniakDepartment of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52242;
Susan A WalshDepartment of Radiology, University of Iowa Carver College of Medicine, Iowa City, IA 52242;
Michael R AcevedoDepartment of Radiology, University of Iowa Carver College of Medicine, Iowa City, IA 52242;
Carmen M Perez-TerzicDepartment of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, MN 55905;
Denice M Hodgson-ZingmanDepartment of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52242; Fraternal Order of Eagles Diabetes Research Center, University of Iowa Carver College of Medicine, Iowa City, IA 52242; leonid-zingman@uiowa.edu denice-zingman@uiowa.edu.
Leonid V ZingmanDepartment of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52242; Fraternal Order of Eagles Diabetes Research Center, University of Iowa Carver College of Medicine, Iowa City, IA 52242; Department of Medicine, Medical Center, Department of Veterans Affairs, Iowa City, IA 52242 leonid-zingman@uiowa.edu denice-zingman@uiowa.edu.
University of Iowa · USMayo Clinic in Arizona · USFraternal Order of Eagles · US

Funding

Control of KATP channel expression by CaMKII: role in heart failure resistanceR01HL113089 · NHLBI · UNIVERSITY OF IOWA · PI HODGSON-ZINGMAN, DENICE · 2012 to 2016
$1.9M
Skeletal muscle KATP channels determine bodily energy balanceR01DK092412 · NIDDK · UNIVERSITY OF IOWA · PI ZINGMAN, LEONID · 2012 to 2016
$1.6M
KATP channel regulation of bodily energy expenditure and weight maintenanceK08HL093368 · NHLBI · UNIVERSITY OF IOWA · PI ZINGMAN, LEONID · 2008 to 2012
$637k
Skeletal muscle ATP-sensitive potassium channels determine bodily energy balanceI01BX000718 · VA · IOWA CITY VA MEDICAL CENTER · PI ZINGMAN, LEONID · 2011 to 2015
–
BLRD VA I01 BX000718NHLBI NIH HHS HL093368NHLBI NIH HHS HL113089NHLBI NIH HHS K08 HL093368NHLBI NIH HHS R01 HL113089NIDDK NIH HHS DK092412NIDDK NIH HHS R01 DK092412
6 · The paper itself

Abstract

Exercise remains the most effective way to promote physical and metabolic wellbeing, but molecular mechanisms underlying exercise tolerance and its plasticity are only partially understood. In this study we identify musclin-a peptide with high homology to natriuretic peptides (NP)-as an exercise-responsive myokine that acts to enhance exercise capacity in mice. We use human primary myoblast culture and in vivo murine models to establish that the activity-related production of musclin is driven by Ca(2+)-dependent activation of Akt1 and the release of musclin-encoding gene (Ostn) transcription from forkhead box O1 transcription factor inhibition. Disruption of Ostn and elimination of musclin secretion in mice results in reduced exercise tolerance that can be rescued by treatment with recombinant musclin. Reduced exercise capacity in mice with disrupted musclin signaling is associated with a trend toward lower levels of plasma atrial NP (ANP) and significantly smaller levels of cyclic guanosine monophosphate (cGMP) and peroxisome proliferator-activated receptor gamma coactivator 1-α in skeletal muscles after exposure to exercise. Furthermore, in agreement with the established musclin ability to interact with NP clearance receptors, but not with NP guanyl cyclase-coupled signaling receptors, we demonstrate that musclin enhances cGMP production in cultured myoblasts only when applied together with ANP. Elimination of the activity-related musclin-dependent boost of ANP/cGMP signaling results in significantly lower maximum aerobic capacity, mitochondrial protein content, respiratory complex protein expression, and succinate dehydrogenase activity in skeletal muscles. Together, these data indicate that musclin enhances physical endurance by promoting mitochondrial biogenesis.

Indexed as

Physical Conditioning, AnimalAnimalsAtrial Natriuretic FactorBlotting, WesternCalcimycinCalciumCalcium IonophoresCells, CulturedCyclic GMPFemaleForkhead Box Protein O1Forkhead Transcription FactorsHumansMaleMice, Inbred C57BLMice, KnockoutAkt1 protein, mouseAtrial Natriuretic FactorCalcimycinCalciumCalcium IonophoresCyclic GMPForkhead Box Protein O1Forkhead Transcription FactorsFoxo1 protein, mouseMuscle ProteinsOstn protein, mouseProto-Oncogene Proteins c-aktTranscription Factorsexercisemitochondrianatriuretic peptideosteocrinskeletal muscle

Identifiers

PMID26668395
PMCPMC4702977
OpenAlexW2221507346

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.