It is now widely accepted that hypertension and endothelial dysfunction are associated with an insulin-resistant state and thus with the development of T2DM (Type 2 diabetes mellitus). Insulin signalling is impaired in target cells and tissues, indicating that common molecular signals are involved. The free radical NO• regulates cell metabolism, insulin signalling and secretion, vascular tone, neurotransmission and immune system function. NO• synthesis is essential for vasodilation, the maintenance of blood pressure and glucose uptake and, thus, if levels of NO• are decreased, insulin resistance and hypertension will result. Decreased blood levels of insulin, increased AngII (angiotensin II), hyperhomocysteinaemia, increased ADMA (asymmetric ω-NG,NG-dimethylarginine) and low plasma L-arginine are all conditions likely to decrease NO• production and which are associated with diabetes and cardiovascular disease. We suggest in the present article that the widely reported beneficial effects of exercise in the improvement of metabolic and cardiovascular health are mediated by enhancing the flux of muscle- and kidney-derived amino acids to pancreatic and vascular endothelial cells aiding the intracellular production of NO•, therefore resulting in normalization of insulin secretion, vascular tone and insulin sensitivity. Exercise may also have an impact on AngII and ADMA signalling and the production of pro- and anti-inflammatory cytokines in muscle, so reducing the progression and development of vascular disease and diabetes. NO• synthesis will be increased during exercise in the vascular endothelial cells so promoting blood flow. We suggest that exercise may promote improvements in health due to positive metabolic and cytokine-mediated effects.
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Hypothesis|
November 23 2009
Exercise and possible molecular mechanisms of protection from vascular disease and diabetes: the central role of ROS and nitric oxide
Philip Newsholme;
*School of Biomolecular and Biomedical Science, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland
†UCD Institute for Sport and Health, University College Dublin, Belfield, Dublin 4, Ireland
Correspondence: Professor Philip Newsholme (email [email protected]).
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Paulo I. Homem De Bittencourt, Jr;
Paulo I. Homem De Bittencourt, Jr
‡Department of Physiology, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul and Federal University of Rio Grande do Sul School of Physical Education, Porto Alegre, RS, Brazil
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Ciara O' Hagan;
Ciara O' Hagan
†UCD Institute for Sport and Health, University College Dublin, Belfield, Dublin 4, Ireland
§School of Physiotherapy and Performance Science, University College Dublin, Belfield, Dublin 4, Ireland
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Giuseppe De Vito;
Giuseppe De Vito
†UCD Institute for Sport and Health, University College Dublin, Belfield, Dublin 4, Ireland
§School of Physiotherapy and Performance Science, University College Dublin, Belfield, Dublin 4, Ireland
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Colin Murphy;
Colin Murphy
∥Biomedical Research Group (BMRG), Department of Science, Institute of Technology Tallaght, Dublin 24, Ireland
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Mauricio S. Krause
Mauricio S. Krause
*School of Biomolecular and Biomedical Science, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland
†UCD Institute for Sport and Health, University College Dublin, Belfield, Dublin 4, Ireland
∥Biomedical Research Group (BMRG), Department of Science, Institute of Technology Tallaght, Dublin 24, Ireland
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Publisher: Portland Press Ltd
Received:
August 17 2009
Revision Received:
October 06 2009
Accepted:
October 08 2009
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2010 Biochemical Society
2010
Clin Sci (Lond) (2010) 118 (5): 341–349.
Article history
Received:
August 17 2009
Revision Received:
October 06 2009
Accepted:
October 08 2009
Citation
Philip Newsholme, Paulo I. Homem De Bittencourt, Ciara O' Hagan, Giuseppe De Vito, Colin Murphy, Mauricio S. Krause; Exercise and possible molecular mechanisms of protection from vascular disease and diabetes: the central role of ROS and nitric oxide. Clin Sci (Lond) 1 March 2010; 118 (5): 341–349. doi: https://doi.org/10.1042/CS20090433
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