Evidence mapPaperPMID 21873552Full record

ArticleDiabetes2011

Skeletal muscle triglycerides, diacylglycerols, and ceramides in insulin resistance: another paradox in endurance-trained athletes?

Francesca Amati, John J Dubé, Elvis Alvarez-Carnero, Martin M Edreira, Peter Chomentowski, Paul M Coen, Galen E Switzer, Perry E Bickel, Maja Stefanovic-Racic, Frederico G S Toledo and 1 more

3 registry-linked trialsOpen access · bronzeAbstract read
In one paragraph

Article in Diabetes, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 217 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
217citing papers in PubMed, 2 pooled it
15.8field-weighted citation impact, top 1% 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.

NCT07065383 narecruitingstarted 2025, after this paper: background citation

Intramyocellular Lipid Compartments After Glucagon-like Peptide 1 Receptor Agonist Therapy in Type 2 Diabetes - Rebalancing the Fat Content of the Heart and Muscles

Ran2025Enrolled60Registered outcomes2Posted comparisons0ConditionsDiabetes Mellitus Type 2ArmsSemaglutide administration plus dietary counselling and physical activity encouragement, Semaglutide plus a personalised and supervised program of resistance and endurance training
Open the trial in the graph
NCT02417428 nacompletednot on this mapstarted 2015, after this paper: background citation

Effects of Citrulline Supplementation Combined With Exercise on Muscle Function and Functional Capacity in Older Obese Men and Women

TypeinterventionalSponsorUniversité du Québec a MontréalRan2015 to 2018Enrolled104ConditionsSarcopenia, ObesityArmsCitrulline, Placebo, Exercise, without exercise
NCT03065140 nacompletednot on this mapstarted 2016, after this paper: background citation

Muscle Fat Compartments and Turnover as Determinant of Insulin Sensitivity - the MISTY Study

TypeinterventionalSponsorUniversity of AberdeenRan2016 to 2019Enrolled50ConditionsDiabetesArmsTraining or detraining
3 · Its place in the literature

Who cites it

217 citing papers in PubMed, 2 syntheses or guidelines pooled it, 384 citations in OpenAlex.

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157 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

11 authors at 3 institutions in 2 countries.

Francesca AmatiDepartment of Medicine, Division of Endocrinology and Metabolism, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
John J Dubé
Elvis Alvarez-Carnero
Martin M Edreira
Peter Chomentowski
Paul M Coen
Galen E Switzer
Perry E Bickel
Maja Stefanovic-Racic
Frederico G S Toledo
Bret H Goodpaster
University of Pittsburgh · USThe University of Texas Health Science Center at Houston · USUniversity of Lausanne · CH

Funding

SKELETAL MUSCLE FREE FATTY ACID UPTAKE AND OXIDATION IN OBESITYP30DK046204 · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 1992 to 2005
$5.1M
TECHNOLOGY COREP30AG024827 · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2004 to 2025
$4.3M
Trafficking of Triacylglycerol in AdipocytesR01DK068046 · WASHINGTON UNIVERSITY · 2005 to 2005
$268k
NCRR NIH HHS UL1 RR024153NIA NIH HHS P30 AG024827NIA NIH HHS R01-AG20128NIDDK NIH HHS 1P30DK46204NIDDK NIH HHS P30 DK046204NIDDK NIH HHS R01 DK068046NIDDK NIH HHS R01-DK068046
6 · The paper itself

Abstract

objectiveChronic exercise and obesity both increase intramyocellular triglycerides (IMTGs) despite having opposing effects on insulin sensitivity. We hypothesized that chronically exercise-trained muscle would be characterized by lower skeletal muscle diacylglycerols (DAGs) and ceramides despite higher IMTGs and would account for its higher insulin sensitivity. We also hypothesized that the expression of key skeletal muscle proteins involved in lipid droplet hydrolysis, DAG formation, and fatty-acid partitioning and oxidation would be associated with the lipotoxic phenotype. RESEARCH DESIGN AND

methodsA total of 14 normal-weight, endurance-trained athletes (NWA group) and 7 normal-weight sedentary (NWS group) and 21 obese sedentary (OBS group) volunteers were studied. Insulin sensitivity was assessed by glucose clamps. IMTGs, DAGs, ceramides, and protein expression were measured in muscle biopsies.

resultsDAG content in the NWA group was approximately twofold higher than in the OBS group and ~50% higher than in the NWS group, corresponding to higher insulin sensitivity. While certain DAG moieties clearly were associated with better insulin sensitivity, other species were not. Ceramide content was higher in insulin-resistant obese muscle. The expression of OXPAT/perilipin-5, adipose triglyceride lipase, and stearoyl-CoA desaturase protein was higher in the NWA group, corresponding to a higher mitochondrial content, proportion of type 1 myocytes, IMTGs, DAGs, and insulin sensitivity.

conclusionsTotal myocellular DAGs were markedly higher in highly trained athletes, corresponding with higher insulin sensitivity, and suggest a more complex role for DAGs in insulin action. Our data also provide additional evidence in humans linking ceramides to insulin resistance. Finally, this study provides novel evidence supporting a role for specific skeletal muscle proteins involved in intramyocellular lipids, mitochondrial oxidative capacity, and insulin resistance.

Indexed as

AthletesAgedCeramidesDiglyceridesFemaleHumansInsulinInsulin ResistanceMaleMiddle AgedMitochondria, MuscleMuscle, SkeletalObesityOxygen ConsumptionPhysical EnduranceTriglyceridesCeramidesDiglyceridesInsulinTriglycerides

Identifiers

PMID21873552
PMCPMC3178290
OpenAlexW2032345647

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

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.