Nerve damage induced skeletal muscle atrophy is associated with increased accumulation of intramuscular glucose and polyol pathway intermediates.
Animals
Disease Models, Animal
Glucose
/ metabolism
Glucose Transporter Type 1
/ metabolism
Glucose Transporter Type 4
/ metabolism
Glycogen
/ biosynthesis
Glycolysis
Humans
Male
Metabolomics
Muscle, Skeletal
/ innervation
Muscular Atrophy
/ etiology
Peripheral Nerve Injuries
/ complications
Polymers
/ metabolism
Rats
Sciatic Nerve
/ injuries
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
05 02 2020
05 02 2020
Historique:
received:
01
08
2019
accepted:
23
12
2019
entrez:
7
2
2020
pubmed:
7
2
2020
medline:
21
11
2020
Statut:
epublish
Résumé
Perturbations in skeletal muscle metabolism have been reported for a variety of neuromuscular diseases. However, the role of metabolism after constriction injury to a nerve and the associated muscle atrophy is unclear. We have analyzed rat tibialis anterior (TA) four weeks after unilateral constriction injury to the sciatic nerve (DMG) and in the contralateral control leg (CTRL) (n = 7) to investigate changes of the metabolome, immunohistochemistry and protein levels. Untargeted metabolomics identified 79 polar metabolites, 27 of which were significantly altered in DMG compared to CTRL. Glucose concentrations were increased 2.6-fold in DMG, while glucose 6-phosphate (G6-P) was unchanged. Intermediates of the polyol pathway were increased in DMG, particularly fructose (1.7-fold). GLUT4 localization was scattered as opposed to clearly at the sarcolemma. Despite the altered localization, we found GLUT4 protein levels to be increased 7.8-fold while GLUT1 was decreased 1.7-fold in nerve damaged TA. PFK1 and GS levels were both decreased 2.1-fold, indicating an inability of glycolysis and glycogen synthesis to process glucose at sufficient rates. In conclusion, chronic nerve constriction causes increased GLUT4 levels in conjunction with decreased glycolytic activity and glycogen storage in skeletal muscle, resulting in accumulation of intramuscular glucose and polyol pathway intermediates.
Identifiants
pubmed: 32024865
doi: 10.1038/s41598-020-58213-1
pii: 10.1038/s41598-020-58213-1
pmc: PMC7002415
doi:
Substances chimiques
Glucose Transporter Type 1
0
Glucose Transporter Type 4
0
Polymers
0
Slc2a1 protein, rat
0
Slc2a4 protein, rat
0
polyol
0
Glycogen
9005-79-2
Glucose
IY9XDZ35W2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1908Références
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