Muscle-specific AXIN1 and AXIN2 double knockout does not alter AMPK/mTORC1 signalling or glucose metabolism

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dc.contributor.authorPersson, Kaspar W.
dc.contributor.authorMeneses-Valdés, Roberto
dc.contributor.authorAndersen, Nicoline R.
dc.contributor.authorPedersen, Frederik S.
dc.contributor.authorGallo, Samantha
dc.contributor.authorHesselager, Sofie A.
dc.contributor.authorHenríquez-Olguín, Carlos
dc.contributor.authorJensen, Thomas E.
dc.date.accessioned2025-10-29T11:57:59Z
dc.date.available2025-10-29T11:57:59Z
dc.date.issued2025-07-01
dc.description.abstractAMP-activated protein kinase (AMPK) and mechanistic target of rapamycin complex 1 (mTORC1) are crucial kinase signalling hubs that regulate the balance between catabolism and anabolism in skeletal muscle. The scaffold protein AXIN1 has been proposed to regulate the switch between these pathways and be required for GLUT4 translocation in skeletal muscle and adipocyte cell lines. Muscle-specific AXIN1 knockout (KO) mice exhibit no discernable phenotype, possibly due to compensation by AXIN2 upon AXIN1 loss. Thus we generated and characterized muscle-specific inducible AXIN1 and AXIN2 double knockout (dKO) mice. Surprisingly AXIN1/2 dKO mice displayed normal AMPK and mTORC1 signalling and glucose uptake in response to 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), insulin and in situ muscle contraction. These findings suggest that AXIN proteins are not essential for the regulation of AMPK and mTORC1 signalling or glucose uptake in skeletal muscle. This study challenges the previously indicated critical roles of AXIN1 in exercise-stimulated AMPK activation and GLUT4-mediated glucose uptake in skeletal muscle. KEY POINTS: Phenotyping of tamoxifen-inducible muscle-specific AXIN1/2 double knockout (dKO) mice. We find no evidence for AXIN-dependent AMPK or mTORC1 regulation in skeletal muscle by insulin, AMPK activation or contraction. Glucose uptake regulation by insulin and AMPK activation is normal in AXIN1/2 dKO mice.
dc.identifier.citationThe Journal of Physiology, Vol. 603, N°14 (2025) p. 3961-3971.
dc.identifier.doihttps://doi.org/10.1113/JP288854
dc.identifier.issn0022-3751
dc.identifier.issne1469-7793
dc.identifier.orcidhttps://orcid.org/0000-0002-9315-9365
dc.identifier.urihttps://hdl.handle.net/20.500.12254/4364
dc.language.isoen
dc.publisherWiley; The Physiological Society
dc.rightsAtribución-NoComercial-CompartirIgual 3.0 Chile (CC BY-NC-SA 3.0 CL)
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/3.0/cl/
dc.subjectSkeletal muscle
dc.subjectExercise
dc.subjectAMPK
dc.titleMuscle-specific AXIN1 and AXIN2 double knockout does not alter AMPK/mTORC1 signalling or glucose metabolism
dc.typeArticle
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