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The regulation of metabolic gene expression in human skeletal muscle by exercise: the influence of exercise intensity and contraction frequency

Carson, Brian (2010) The regulation of metabolic gene expression in human skeletal muscle by exercise: the influence of exercise intensity and contraction frequency. PhD thesis, Dublin City University.

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Abstract

Skeletal muscle contraction increases energy expenditure and improves metabolic flexibility, but is also a key regulator of metabolic gene expression. Acute exercise stimulates a unique set of intracellular signalling cascades resulting in the activation of kinases which can subsequently control muscle metabolism. The signalling pathways involved are activated by alterations in ATP turnover, calcium flux, cellular stress and the redox state in the muscle cell. The aim of this thesis was to impact the main variables influencing muscle contraction, the contraction force and frequency, during an acute bout of exercise and to investigate the subsequent outcome of altering these variables on intracellular signalling and metabolic gene expression in human skeletal muscle. High intensity isocaloric exercise (400 kcal, 80%VO2peak) resulted in greater activation of the signalling kinases AMPK and CaMKII than low intensity exercise (40% VO2peak), whereas the frequency of contraction (50 vs 80 RPM) had no effect on AMPK and CaMKII phosphorylation. PGC-1a mRNA was upregulated after exercise with a greater increase observed after high compared to low intensity. PGC-1a mRNA was also regulated by the frequency of contraction with a greater increase observed after exercising at a higher contraction frequency. Exercise induced a response in a number of metabolic genes associated with the regulation of substrate utilisation including FOXO1A and PDK4. This may form part of a transcriptional response to exercise that promotes fat oxidation and glucose sparing in the recovery from exercise. These results suggest that an acute bout of exercise induces a transient response in intracellular signaling and metabolic gene expression in human skeletal muscle specific to the demands placed upon the tissue.

Item Type:Thesis (PhD)
Date of Award:22 September 2010
Refereed:No
Subjects:Medical Sciences > Exercise
Medical Sciences > Physiology
DCU Faculties and Centres:DCU Faculties and Schools > Faculty of Science and Health > School of Health and Human Performance
Use License:This item is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 License. View License
ID Code:15721
Deposited On:04 Apr 2011 16:31 by Donal O'Gorman. Last Modified 04 Apr 2011 16:31

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