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Effects of fasting induced carbohydrate depletion on murine ischemic skeletal muscle function

View ORCID ProfileCameron A. Schmidt, Emma J. Goldberg, Tom D. Green, Reema R. Karnekar, View ORCID ProfileJeffrey J. Brault, Spencer G. Miller, Adam J. Amorese, Dean J. Yamaguchi, Espen E. Spangenburg, Joseph M. McClung
doi: https://doi.org/10.1101/846774
Cameron A. Schmidt
1Dept. of Physiology, Brody School of Medicine, East Carolina University, Greenville, North Carolina, United States of America
2East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, North Carolina, United States of America
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  • ORCID record for Cameron A. Schmidt
Emma J. Goldberg
1Dept. of Physiology, Brody School of Medicine, East Carolina University, Greenville, North Carolina, United States of America
2East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, North Carolina, United States of America
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Tom D. Green
1Dept. of Physiology, Brody School of Medicine, East Carolina University, Greenville, North Carolina, United States of America
2East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, North Carolina, United States of America
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Reema R. Karnekar
1Dept. of Physiology, Brody School of Medicine, East Carolina University, Greenville, North Carolina, United States of America
2East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, North Carolina, United States of America
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Jeffrey J. Brault
1Dept. of Physiology, Brody School of Medicine, East Carolina University, Greenville, North Carolina, United States of America
3Dept. of Kinesiology, College of Health and Human Performance, East Carolina University, Greenville, North Carolina, United States of America
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  • ORCID record for Jeffrey J. Brault
Spencer G. Miller
3Dept. of Kinesiology, College of Health and Human Performance, East Carolina University, Greenville, North Carolina, United States of America
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Adam J. Amorese
1Dept. of Physiology, Brody School of Medicine, East Carolina University, Greenville, North Carolina, United States of America
2East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, North Carolina, United States of America
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Dean J. Yamaguchi
4Department of Cardiovascular Sciences, East Carolina University, Greenville, North Carolina, United States of America
5Division of Surgery, Brody School of Medicine, East Carolina University, Greenville, North Carolina, United States of America
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Espen E. Spangenburg
1Dept. of Physiology, Brody School of Medicine, East Carolina University, Greenville, North Carolina, United States of America
2East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, North Carolina, United States of America
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Joseph M. McClung
1Dept. of Physiology, Brody School of Medicine, East Carolina University, Greenville, North Carolina, United States of America
2East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, North Carolina, United States of America
4Department of Cardiovascular Sciences, East Carolina University, Greenville, North Carolina, United States of America
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  • For correspondence: mcclungj@ecu.edu
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Abstract

Stored muscle carbohydrate supply and energetic efficiency constrain muscle functional capacity during exercise and are influenced by common physiological variables (e.g. age, diet, and physical activity level). Whether these constraints affect overall functional capacity or the timing of muscle energetic failure during acute ischemia is not known. We interrogated skeletal muscle contractile properties in two anatomically distinct hindlimb muscles that have well characterized differences in energetic efficiency (locomotory-extensor digitorum longus (EDL) and postural-soleus muscles) under conditions of reduced carbohydrate supply. 180 mins of acute ischemia resulted in complete energetic failure in all muscles tested, indicated by: loss of force production, substantial reductions in total adenosine nucleotide pool intermediates, and increased adenosine nucleotide degradation product - inosine monophosphate (IMP). These changes occurred in the absence of apparent myofiber structural damage assessed histologically by both transverse section and whole mount. Restriction of the available intracellular carbohydrate pool by fasting (~50% decrease in skeletal muscle) did not significantly alter the timing to muscle functional impairment or affect the overall force/work capacities of either muscle type. Fasting did cause rapid development of passive tension in both muscle types, which may have implications for optimal timing of reperfusion or administration of precision therapeutics.

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Posted November 18, 2019.
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Effects of fasting induced carbohydrate depletion on murine ischemic skeletal muscle function
Cameron A. Schmidt, Emma J. Goldberg, Tom D. Green, Reema R. Karnekar, Jeffrey J. Brault, Spencer G. Miller, Adam J. Amorese, Dean J. Yamaguchi, Espen E. Spangenburg, Joseph M. McClung
bioRxiv 846774; doi: https://doi.org/10.1101/846774
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Effects of fasting induced carbohydrate depletion on murine ischemic skeletal muscle function
Cameron A. Schmidt, Emma J. Goldberg, Tom D. Green, Reema R. Karnekar, Jeffrey J. Brault, Spencer G. Miller, Adam J. Amorese, Dean J. Yamaguchi, Espen E. Spangenburg, Joseph M. McClung
bioRxiv 846774; doi: https://doi.org/10.1101/846774

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