AXIN1 knockout does not alter AMPK/mTORC1 regulation and glucose metabolism in mouse skeletal muscle.
AMP-Activated Protein Kinases
/ metabolism
Aminoimidazole Carboxamide
Animals
Axin Protein
/ genetics
Energy Metabolism
Glucose
/ metabolism
Insulin
Mechanistic Target of Rapamycin Complex 1
Mice
Mice, Knockout
Muscle Contraction
Muscle, Skeletal
/ physiology
Physical Conditioning, Animal
Ribonucleotides
AMPK
exercise
glucose metabolism
insulin
mTORC1
Journal
The Journal of physiology
ISSN: 1469-7793
Titre abrégé: J Physiol
Pays: England
ID NLM: 0266262
Informations de publication
Date de publication:
06 2021
06 2021
Historique:
received:
03
12
2020
accepted:
20
04
2021
pubmed:
30
4
2021
medline:
8
7
2021
entrez:
29
4
2021
Statut:
ppublish
Résumé
Tamoxifen-inducible skeletal muscle-specific AXIN1 knockout (AXIN1 imKO) in mouse does not affect whole-body energy substrate metabolism. AXIN1 imKO does not affect AICAR or insulin-stimulated glucose uptake in adult skeletal muscle. AXIN1 imKO does not affect adult skeletal muscle AMPK or mTORC1 signalling during AICAR/insulin/amino acid incubation, contraction and exercise. During exercise, α2/β2/γ3AMPK and AMP/ATP ratio show greater increases in AXIN1 imKO than wild-type in gastrocnemius muscle. AXIN1 is a scaffold protein known to interact with >20 proteins in signal transduction pathways regulating cellular development and function. Recently, AXIN1 was proposed to assemble a protein complex essential to catabolic-anabolic transition by coordinating AMPK activation and inactivation of mTORC1 and to regulate glucose uptake-stimulation by both AMPK and insulin. To investigate whether AXIN1 is permissive for adult skeletal muscle function, a phenotypic in vivo and ex vivo characterization of tamoxifen-inducible skeletal muscle-specific AXIN1 knockout (AXIN1 imKO) mice was conducted. AXIN1 imKO did not influence AMPK/mTORC1 signalling or glucose uptake stimulation at rest or in response to different exercise/contraction protocols, pharmacological AMPK activation, insulin or amino acids stimulation. The only genotypic difference observed was in exercising gastrocnemius muscle, where AXIN1 imKO displayed elevated α2/β2/γ3 AMPK activity and AMP/ATP ratio compared to wild-type mice. Our work shows that AXIN1 imKO generally does not affect skeletal muscle AMPK/mTORC1 signalling and glucose metabolism, probably due to functional redundancy of its homologue AXIN2.
Substances chimiques
Axin Protein
0
Axin1 protein, mouse
0
Insulin
0
Ribonucleotides
0
Aminoimidazole Carboxamide
360-97-4
Mechanistic Target of Rapamycin Complex 1
EC 2.7.11.1
AMP-Activated Protein Kinases
EC 2.7.11.31
Glucose
IY9XDZ35W2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3081-3100Informations de copyright
© 2021 The Authors. The Journal of Physiology © 2021 The Physiological Society.
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