Related Experiment Video

Updated: Sep 17, 2025

Measurement of Insulin- and Contraction-Stimulated Glucose Uptake in Isolated and Incubated Mature Skeletal Muscle from Mice
08:01

Measurement of Insulin- and Contraction-Stimulated Glucose Uptake in Isolated and Incubated Mature Skeletal Muscle from Mice

Published on: May 16, 2021

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

Kaspar W Persson1, Roberto Meneses-Valdés1, Nicoline R Andersen1

  • 1August Krogh Section for Human and Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark.

The Journal of Physiology
|June 30, 2025
PubMed

Insights

AXIN1 and AXIN2 proteins do not appear essential for regulating skeletal muscle metabolism. Muscle-specific knockout mice lacking both AXIN1 and AXIN2 showed normal glucose uptake and signaling pathways, challenging prior assumptions.

Area of Science:

  • Skeletal Muscle Physiology
  • Molecular Signaling
  • Metabolic Regulation

Background:

  • AMP-activated protein kinase (AMPK) and mTORC1 are key regulators of skeletal muscle catabolism and anabolism.
  • AXIN1 was previously proposed to control the switch between these pathways and facilitate GLUT4 translocation.
  • Muscle-specific AXIN1 knockout mice showed no phenotype, suggesting AXIN2 might compensate.

Purpose of the Study:

  • To investigate the role of AXIN1 and AXIN2 in skeletal muscle metabolism.
  • To determine if AXIN proteins are essential for AMPK and mTORC1 signaling.
  • To assess the impact of AXIN1/2 loss on glucose uptake in response to various stimuli.

Main Methods:

  • Generation of tamoxifen-inducible muscle-specific AXIN1 and AXIN2 double knockout (dKO) mice.
  • Phenotyping of dKO mice to assess physiological responses.
  • Measurement of AMPK and mTORC1 signaling pathways.
  • Assessment of glucose uptake via GLUT4 translocation in response to insulin, AICAR, and muscle contraction.

Main Results:

  • AXIN1/2 dKO mice exhibited normal AMPK and mTORC1 signaling.
  • Glucose uptake in response to AICAR, insulin, and muscle contraction was unaffected in dKO mice.
  • These findings indicate no essential role for AXIN proteins in these metabolic processes.

Conclusions:

  • AXIN proteins are not essential for regulating AMPK and mTORC1 signaling in skeletal muscle.
  • The previously suggested roles of AXIN1 in exercise-stimulated AMPK activation and GLUT4 glucose uptake are challenged.
  • Skeletal muscle metabolism and glucose uptake are regulated independently of AXIN1 and AXIN2.
Keywords:
AMPKexerciseglucose transportmTORskeletal muscle

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