AXIN1 knockout does not alter AMPK/mTORC1 regulation and glucose metabolism in mouse skeletal muscle

Jingwen Li, Jonas Roland Knudsen, Carlos Henriquez-Olguin, Zhencheng Li, Jesper Bratz Birk, Kaspar Wredstrøm Persson, Ylva Hellsten, Anika Offergeld, William Jarassier, Fabien L Grand, Peter Schjerling, Jørgen Wojtaszewski, Thomas Elbenhardt Jensen*

*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

6 Citationer (Scopus)

Abstract

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 signaling or glucose uptake stimulation, neither at rest nor 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 signaling and glucose metabolism, likely due to functional redundancy of its homolog AXIN2. 

OriginalsprogEngelsk
TidsskriftJournal of Physiology
Vol/bind599
Udgave nummer12
Sider (fra-til)3081-3100
Antal sider20
ISSN0022-3751
DOI
StatusUdgivet - 2021

Bibliografisk note

CURIS 2021 NEXS 178

Citationsformater