期刊
JOURNAL OF PHYSIOLOGY-LONDON
卷 599, 期 12, 页码 3081-3100出版社
WILEY
DOI: 10.1113/JP281187
关键词
AMPK; exercise; glucose metabolism; insulin; mTORC1
资金
- Novo Nordisk Foundation (NNF) [15182, NNF19OC0056839]
- Lundbeck Foundation [R313-2019-643]
- Danish Research Medical Council [FSS8020-00288B]
- China Scholarship Council (CSC) [201707940001]
- Independent Research Fund Denmark [9058-00047B]
- Danish Diabetes Academy by Novo Nordisk Foundation [NNF17SA0031406]
AXIN1 imKO does not affect whole-body energy metabolism, AMPK/mTORC1 signaling, or glucose uptake in skeletal muscle, showing only differences in exercising gastrocnemius muscle.
Key points 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, alpha 2/beta 2/gamma 3AMPK 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 alpha 2/beta 2/gamma 3 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.
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