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Mol Genet Metab. 2018 Jan;123(1):21-27. doi: 10.1016/j.ymgme.2017.11.006. Epub 2017 Nov 21.

Exercising with blocked muscle glycogenolysis: Adaptation in the McArdle mouse.

Author information

1
Copenhagen Neuromuscular Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
2
Mitochondrial Pathology and Neuromuscular Disorders Laboratory, Vall d'Hebron Research Institute, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Spain.
3
Sorbonne Universités, UPMC Univ Paris 06, INSERM UMRS_974, CNRS FRE 3617, Center of Research in Myology, F-75013 Paris, France.
4
Copenhagen Neuromuscular Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. Electronic address: thomas.krag@regionh.dk.

Abstract

BACKGROUND:

McArdle disease (glycogen storage disease type V) is an inborn error of skeletal muscle metabolism, which affects glycogen phosphorylase (myophosphorylase) activity leading to an inability to break down glycogen. Patients with McArdle disease are exercise intolerant, as muscle glycogen-derived glucose is unavailable during exercise. Metabolic adaptation to blocked muscle glycogenolysis occurs at rest in the McArdle mouse model, but only in highly glycolytic muscle. However, it is unknown what compensatory metabolic adaptations occur during exercise in McArdle disease.

METHODS:

In this study, 8-week old McArdle and wild-type mice were exercised on a treadmill until exhausted. Dissected muscles were compared with non-exercised, age-matched McArdle and wild-type mice for histology and activation and expression of proteins involved in glucose uptake and glycogenolysis.

RESULTS:

Investigation of expression and activation of proteins involved in glycolytic flux revealed that in glycolytic, but not oxidative muscle from exercised McArdle mice, the glycolytic flux had changed compared to that in wild-type mice. Specifically, exercise triggered in glycolytic muscle a differentiated activation of insulin receptor, 5' adenosine monophosphate-activated protein kinase, Akt and hexokinase II expression, while inhibiting glycogen synthase, suggesting that the need and adapted ability to take up blood glucose and use it for metabolism or glycogen storage is different among the investigated muscles.

CONCLUSION:

The main finding of the study is that McArdle mouse muscles appear to adapt to the energy crisis by increasing expression and activation of proteins involved in blood glucose metabolism in response to exercise in the same directional way across the investigated muscles.

KEYWORDS:

AMPK; Glycogen; Insulin receptor; McArdle mouse

PMID:
29174367
DOI:
10.1016/j.ymgme.2017.11.006
[Indexed for MEDLINE]

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