Evidence map›Paper›PMID 27044864›Full record

ArticleMolecular and cellular biology2016

Nrf2-Mediated Regulation of Skeletal Muscle Glycogen Metabolism.

Akira Uruno, Yoko Yagishita, Fumiki Katsuoka, Yasuo Kitajima, Aki Nunomiya, Ryoichi Nagatomi, Jingbo Pi, Shyam S Biswal, Masayuki Yamamoto

Open access · bronzeAbstract read
In one paragraph

Article in Molecular and cellular biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.

0numbers the graph read from it
0cells of the map it votes in
73citing papers in PubMed
6.4field-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

73 citing papers in PubMed, 125 citations in OpenAlex.

  1. Article
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  10. Muscle-specific Keap1 deletion enhances force production but does not prevent inactivity-induced muscle atrophy in mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
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  12. Review
  13. Role of NRF2 in Pathogenesis of Alzheimer's Disease.Antioxidants (Basel, Switzerland) · 2024
    Review
  14. Diabetic neuropathy: A NRF2 disease?Journal of diabetes · 2024
    Review
  15. Review
  16. Review
  17. Article
  18. Review
  19. Article
  20. Review

13 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

9 authors at 4 institutions in 3 countries.

Akira UrunoDepartment of Medical Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan uruno@med.tohoku.ac.jp masiyamamoto@med.tohoku.ac.jp.
Yoko YagishitaDepartment of Medical Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
Fumiki KatsuokaDepartment of Integrative Genomics, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Miyagi, Japan.
Yasuo KitajimaDivision of Biomedical Engineering for Health and Welfare, Tohoku University Graduate School of Biomedical Engineering, Sendai, Miyagi, Japan.
Aki NunomiyaDepartment of Medicine and Science in Sports and Exercise, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
Ryoichi NagatomiDivision of Biomedical Engineering for Health and Welfare, Tohoku University Graduate School of Biomedical Engineering, Sendai, Miyagi, Japan.
Jingbo PiSchool of Public Health, China Medical University, Shenyang, Liaoning, China.
Shyam S BiswalDepartment of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.
Masayuki YamamotoDepartment of Medical Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan Department of Integrative Genomics, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Miyagi, Japan uruno@med.tohoku.ac.jp masiyamamoto@med.tohoku.ac.jp.
Tohoku University · JPChina Medical University · CNJohns Hopkins University · USTohoku Medical Megabank Organization · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Nrf2 (NF-E2-related factor 2) contributes to the maintenance of glucose homeostasis in vivo Nrf2 suppresses blood glucose levels by protecting pancreatic β cells from oxidative stress and improving peripheral tissue glucose utilization. To elucidate the molecular mechanisms by which Nrf2 contributes to the maintenance of glucose homeostasis, we generated skeletal muscle (SkM)-specific Keap1 knockout (Keap1MuKO) mice that express abundant Nrf2 in their SkM and then examined Nrf2 target gene expression in that tissue. In Keap1MuKO mice, blood glucose levels were significantly downregulated and the levels of the glycogen branching enzyme (Gbe1) and muscle-type PhKα subunit (Phka1) mRNAs, along with those of the glycogen branching enzyme (GBE) and the phosphorylase b kinase α subunit (PhKα) protein, were significantly upregulated in mouse SkM. Consistent with this result, chemical Nrf2 inducers promoted Gbe1 and Phka1 mRNA expression in both mouse SkM and C2C12 myotubes. Chromatin immunoprecipitation analysis demonstrated that Nrf2 binds the Gbe1 and Phka1 upstream promoter regions. In Keap1MuKO mice, muscle glycogen content was strongly reduced and forced GBE expression in C2C12 myotubes promoted glucose uptake. Therefore, our results demonstrate that Nrf2 induction in SkM increases GBE and PhKα expression and reduces muscle glycogen content, resulting in improved glucose tolerance. Our results also indicate that Nrf2 differentially regulates glycogen metabolism in SkM and the liver.

Indexed as

AnimalsCells, CulturedGene Expression ProfilingGlycogenGlycogen Debranching Enzyme SystemKelch-Like ECH-Associated Protein 1LiverMiceMice, KnockoutMuscle, SkeletalNF-E2-Related Factor 2Oligonucleotide Array Sequence AnalysisPhosphorylase KinasePromoter Regions, GeneticGlycogenGlycogen Debranching Enzyme SystemKeap1 protein, mouseKelch-Like ECH-Associated Protein 1Nfe2l2 protein, mouseNF-E2-Related Factor 2Phosphorylase Kinase

Identifiers

PMID27044864
PMCPMC4959318
OpenAlexW2341191268

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.