Evidence map›Paper›PMID 25218136›Full record

ArticleAmino acids2014

Sepsis-induced changes in amino acid transporters and leucine signaling via mTOR in skeletal muscle.

Lacee J Laufenberg, Anne M Pruznak, Maithili Navaratnarajah, Charles H Lang

Open access · greenAbstract read
In one paragraph

Article in Amino acids, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed, 1 pooled it
2.1field-weighted citation impact, top 13% 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

20 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Sepsis and the immunometabolic inflammatory response.npj metabolic health and disease · 2026
    Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Nutrition Support for Persistent Inflammation, Immunosuppression, and Catabolism Syndrome.Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition · 2017
    Article
  16. Article
  17. Article
  18. Mechanisms of protein balance in skeletal muscle.Domestic animal endocrinology · 2016
    Review
  19. Article
  20. Article
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

4 authors at 2 institutions in 1 country.

Lacee J LaufenbergDepartments of Cellular and Molecular Physiology (H166), and Surgery, Penn State College of Medicine, Hershey, PA, 17033, USA.
Anne M Pruznak
Maithili Navaratnarajah
Charles H Lang
Penn State Milton S. Hershey Medical Center · USPennsylvania State University · US

Funding

SEPSIS INDUCED INSULIN RESISTANCE IN DIABETESR01GM038032 · NIGMS · STATE UNIVERSITY NEW YORK STONY BROOK · PI LANG, CHARLES H. · 1992 to 2015
$5.4M
SEPSIS INDUCED INSULIN RESISTANCE IN DIABETESR29GM038032 · NIGMS · LOUISIANA STATE UNIV HSC NEW ORLEANS · PI LANG, CHARLES H. · 1987 to 1991
–
NIGMS NIH HHS GM38032NIGMS NIH HHS R01 GM038032
6 · The paper itself

Abstract

The present study tested the hypothesis that sepsis-induced leucine (Leu) resistance in skeletal muscle is associated with a down-regulation of amino acid transporters important in regulating Leu flux or an impairment in the formation of the Leu-sensitive mTOR-Ragulator complex. Sepsis in adult male rats decreased basal protein synthesis in gastrocnemius, associated with a reduction in mTOR activation as indicated by decreased 4E-BP1 and S6K1 phosphorylation. The ability of oral Leu to increase protein synthesis and mTOR kinase after 1 h was largely prevented in sepsis. Sepsis increased CAT1, LAT2 and SNAT2 mRNA content two- to fourfold, but only the protein content for CAT1 (20 % decrease) differed significantly. Conversely, sepsis decreased the proton-assisted amino acid transporter (PAT)-2 mRNA by 60 %, but without a coordinate change in PAT2 protein. There was no sepsis or Leu effect on the protein content for RagA-D, LAMTOR-1 and -2, raptor, Rheb or mTOR in muscle. The binding of mTOR, PRAS40 and RagC to raptor did not differ for control and septic muscle in the basal condition; however, the Leu-induced decrease in PRAS40·raptor and increase in RagC·raptor seen in control muscle was absent in sepsis. The intracellular Leu concentration was increased in septic muscle, compared to basal control conditions, and oral Leu further increased the intracellular Leu concentration similarly in both control and septic rats. Hence, while alterations in select amino acid transporters are not associated with development of sepsis-induced Leu resistance, the Leu-stimulated binding of raptor with RagC and the recruitment of mTOR/raptor to the endosome-lysosomal compartment may partially explain the inability of Leu to fully activate mTOR and muscle protein synthesis.

Indexed as

Signal TransductionAmino Acid Transport SystemsAnimalsLeucineMaleMuscle, SkeletalRatsRats, Sprague-DawleySepsisTOR Serine-Threonine KinasesAmino Acid Transport SystemsLeucineTOR Serine-Threonine Kinases

Identifiers

PMID25218136
PMCPMC4367815
OpenAlexW2009070613

What OpenQuestion holds

Textmetadata
LicenceTDM
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.