Exercise and possible molecular mechanisms of protection from vascular disease and diabetes: The central role of ROS and nitric oxide

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....

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Main Authors: Newsholme, Philip, De Bittencourt, P., O'Hagan, C., De Vito, G., Murphy, C., Krause, M.
Format: Journal Article
Published: Portland Press 2010
Online Access:http://hdl.handle.net/20.500.11937/24750
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author Newsholme, Philip
De Bittencourt, P.
O'Hagan, C.
De Vito, G.
Murphy, C.
Krause, M.
author_facet Newsholme, Philip
De Bittencourt, P.
O'Hagan, C.
De Vito, G.
Murphy, C.
Krause, M.
author_sort Newsholme, Philip
building Curtin Institutional Repository
collection Online Access
description 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 ?-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. © The Authors Journal compilation © 2010 Biochemical Society.
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publishDate 2010
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spelling curtin-20.500.11937-247502017-09-13T15:13:59Z Exercise and possible molecular mechanisms of protection from vascular disease and diabetes: The central role of ROS and nitric oxide Newsholme, Philip De Bittencourt, P. O'Hagan, C. De Vito, G. Murphy, C. Krause, M. 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 ?-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. © The Authors Journal compilation © 2010 Biochemical Society. 2010 Journal Article http://hdl.handle.net/20.500.11937/24750 10.1042/CS20090433 Portland Press unknown
spellingShingle Newsholme, Philip
De Bittencourt, P.
O'Hagan, C.
De Vito, G.
Murphy, C.
Krause, M.
Exercise and possible molecular mechanisms of protection from vascular disease and diabetes: The central role of ROS and nitric oxide
title Exercise and possible molecular mechanisms of protection from vascular disease and diabetes: The central role of ROS and nitric oxide
title_full Exercise and possible molecular mechanisms of protection from vascular disease and diabetes: The central role of ROS and nitric oxide
title_fullStr Exercise and possible molecular mechanisms of protection from vascular disease and diabetes: The central role of ROS and nitric oxide
title_full_unstemmed Exercise and possible molecular mechanisms of protection from vascular disease and diabetes: The central role of ROS and nitric oxide
title_short Exercise and possible molecular mechanisms of protection from vascular disease and diabetes: The central role of ROS and nitric oxide
title_sort exercise and possible molecular mechanisms of protection from vascular disease and diabetes: the central role of ros and nitric oxide
url http://hdl.handle.net/20.500.11937/24750