Elevated GLUT4 and glycogenin protein abundance correspond to increased glycogen content in the soleus muscle of mdx mice with no benefit associated with taurine supplementation

Elevated GLUT4 and glycogenin protein abundance correspond to increased glycogen content in the... Duchenne muscular dystrophy (DMD) patients and the dystrophic mdx mouse have an elevated demand for ATP requiring processes, including Ca2+ regulation and skeletal muscle regeneration. As a key substrate for cellular ATP production, altered glycogen metabolism may contribute significantly to dystrophic pathology and explain reports of mild glucose intolerance. We compare the soleus and extensor digitorum longus (EDL) muscles of the mdx mouse during active muscle necrosis (at 28 days) and at 70 days where pathology is stable. We further investigate the impact of taurine (tau) on dystrophic glycogen metabolism to identify if the benefit seen with tau in a previous study (Barker et al. ) was in part owed to altered glycogen handling. The soleus muscle of 28‐ and 70‐day‐old mdx mice had elevated glucose transporter type 4 (GLUT4), glycogenin protein abundances and glycogen content compared to WT (C57BL10/ScSn) controls. Mdx tau mice exhibited modestly reduced glycogen compared to their respective mdx group. The EDL muscle of 28 days mdx tau mice had a ~70% increase in glycogenin protein abundance compared to the mdx but 50% less glycogen content. A twofold greater phosphorylated glycogen synthase (p‐GS) and glycogen phosphorylase (p‐GP) protein abundance was observed in the 70‐day‐old mdx soleus muscle than in the 28‐day‐old mdx soleus muscle. Glycogen debranching enzyme (GDE) protein abundance was elevated in both 28‐ and 70‐day‐old mdx soleus muscles compared to WT controls. We identified an increase in proteins associated with glucose uptake and utilization specific to the predominantly slow‐twitch soleus muscle of mdx mice regardless of age and that taurine affords no obvious benefit to glycogen metabolism in the mdx mouse. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Physiological Reports Wiley

Elevated GLUT4 and glycogenin protein abundance correspond to increased glycogen content in the soleus muscle of mdx mice with no benefit associated with taurine supplementation

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Publisher
Wiley Subscription Services, Inc., A Wiley Company
Copyright
© 2018 Published by the American Physiological Society and The Physiological Society
ISSN
2051-817X
eISSN
2051-817X
D.O.I.
10.14814/phy2.13596
Publisher site
See Article on Publisher Site

Abstract

Duchenne muscular dystrophy (DMD) patients and the dystrophic mdx mouse have an elevated demand for ATP requiring processes, including Ca2+ regulation and skeletal muscle regeneration. As a key substrate for cellular ATP production, altered glycogen metabolism may contribute significantly to dystrophic pathology and explain reports of mild glucose intolerance. We compare the soleus and extensor digitorum longus (EDL) muscles of the mdx mouse during active muscle necrosis (at 28 days) and at 70 days where pathology is stable. We further investigate the impact of taurine (tau) on dystrophic glycogen metabolism to identify if the benefit seen with tau in a previous study (Barker et al. ) was in part owed to altered glycogen handling. The soleus muscle of 28‐ and 70‐day‐old mdx mice had elevated glucose transporter type 4 (GLUT4), glycogenin protein abundances and glycogen content compared to WT (C57BL10/ScSn) controls. Mdx tau mice exhibited modestly reduced glycogen compared to their respective mdx group. The EDL muscle of 28 days mdx tau mice had a ~70% increase in glycogenin protein abundance compared to the mdx but 50% less glycogen content. A twofold greater phosphorylated glycogen synthase (p‐GS) and glycogen phosphorylase (p‐GP) protein abundance was observed in the 70‐day‐old mdx soleus muscle than in the 28‐day‐old mdx soleus muscle. Glycogen debranching enzyme (GDE) protein abundance was elevated in both 28‐ and 70‐day‐old mdx soleus muscles compared to WT controls. We identified an increase in proteins associated with glucose uptake and utilization specific to the predominantly slow‐twitch soleus muscle of mdx mice regardless of age and that taurine affords no obvious benefit to glycogen metabolism in the mdx mouse.

Journal

Physiological ReportsWiley

Published: Jan 1, 2018

Keywords: ; ; ; ; ;

References

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