Evidence map›Paper›PMID 21106871›Full record

ArticleEndocrinology2011

Hexose-6-phosphate dehydrogenase contributes to skeletal muscle homeostasis independent of 11β-hydroxysteroid dehydrogenase type 1.

Nina M Semjonous, Mark Sherlock, Pancharatnam Jeyasuria, Keith L Parker, Elizabeth A Walker, Paul M Stewart, Gareth G Lavery

Open access · greenAbstract read
In one paragraph

Article in Endocrinology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed, 1 pooled it
2.4field-weighted citation impact, top 11% 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

36 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Article
  4. Article
  5. Article
  6. G6PC1 and G6PC2 influence G6P flux but not HSD11B1 activity.Journal of molecular endocrinology · 2023
    Article
  7. 11β-HSD1 determines the extent of muscle atrophy in a model of acute exacerbation of COPD.American journal of physiology. Lung cellular and molecular physiology · 2023
    Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  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

7 authors at 3 institutions in 2 countries.

Nina M SemjonousCentre for Endocrinology, Diabetes, and Metabolism, School of Clinical and Experimental Medicine, University of Birmingham, Birmingham UK, B15 2TT, United Kingdom.
Mark Sherlock
Pancharatnam Jeyasuria
Keith L Parker
Elizabeth A Walker
Paul M Stewart
Gareth G Lavery
University of Birmingham · GBMagee-Womens Research Institute · USThe University of Texas Southwestern Medical Center · US

Funding

SF1--KEY MEDIATOR OF ENDOCRINE DEVELOPMENT AND FUNCTIONR01DK054480 · NIDDK · UT SOUTHWESTERN MEDICAL CENTER · PI PARKER, KEITH L. · 1999 to 2007
$2.4M
Biotechnology and Biological Sciences Research Council BB/G023468/1Medical Research Council G0601429NIDDK NIH HHS DK54480NIDDK NIH HHS R01 DK054480Wellcome TrustWellcome Trust 066357
6 · The paper itself

Abstract

Glucose-6-phosphate (G6P) metabolism by the enzyme hexose-6-phosphate dehydrogenase (H6PDH) within the sarcoplasmic reticulum lumen generates nicotinamide adenine dinucleotide phosphate (reduced) to provide the redox potential for the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) to activate glucocorticoid (GC). H6PDH knockout (KO) mice have a switch in 11β-HSD1 activity, resulting in GC inactivation and hypothalamic-pituitary-adrenal axis activation. Importantly, H6PDHKO mice develop a type II fiber myopathy with abnormalities in glucose metabolism and activation of the unfolded protein response (UPR). GCs play important roles in muscle physiology, and therefore, we have examined the importance of 11β-HSD1 and GC metabolism in mediating aspects of the H6PDHKO myopathy. To achieve this, we examined 11β-HSD1/H6PDH double-KO (DKO) mice, in which 11β-HSD1 mediated GC inactivation is negated. In contrast to H6PDHKO mice, DKO mice GC metabolism and hypothalamic-pituitary-adrenal axis set point is similar to that observed in 11β-HSD1KO mice. Critically, in contrast to 11β-HSD1KO mice, DKO mice phenocopy the salient features of the H6PDHKO, displaying reduced body mass, muscle atrophy, and vacuolation of type II fiber-rich muscle, fasting hypoglycemia, increased muscle glycogen deposition, and elevated expression of UPR genes. We propose that muscle G6P metabolism through H6PDH may be as important as changes in the redox environment when considering the mechanism underlying the activation of the UPR and the ensuing myopathy in H6PDHKO and DKO mice. These data are consistent with an 11β-HSD1-independent function for H6PDH in which sarcoplasmic reticulum G6P metabolism and nicotinamide adenine dinucleotide phosphate-(oxidized)/nicotinamide adenine dinucleotide phosphate (reduced) redox status are important for maintaining muscle homeostasis.

Indexed as

11-beta-Hydroxysteroid Dehydrogenase Type 1AnimalsBlood GlucoseCarbohydrate DehydrogenasesCorticosteroneGene Expression Regulation, EnzymologicHomeostasisInsulinMiceMice, KnockoutMuscle, SkeletalMuscular Diseases11-beta-Hydroxysteroid Dehydrogenase Type 1Blood GlucoseCarbohydrate DehydrogenasesCorticosteronegalactose-6-phosphate dehydrogenaseInsulin

Identifiers

PMID21106871
PMCPMC3219053
OpenAlexW1978660595

What OpenQuestion holds

Textmetadata
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.