Siervo, M., Corander, M., Stranges, Saverio and Bluck, L. (2011) Post-challenge hyperglycaemia, nitric oxide production and endothelial dysfunction : the putative role of asymmetric dimethylarginine (ADMA). Nutrition, Metabolism and Cardiovascular Diseases, Vol.21 (No.1). pp. 1-10. doi:10.1016/j.numecd.2010.10.003 ISSN 09394753.
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Abstract
The endothelium is a thin layer of cells at the internal surface of blood vessels in continuous contact with the circulating fluids. The endothelial cells represent the primary barrier for the transport of glucose from the vascular conduits into the interstitial space. Insulin and nitric oxide have an important role in the regulation of glucose transport and metabolism.
Hyperglycaemia is the main criteria for the diagnosis of diabetes and is responsible for the micro- and macro-vascular pathology seen in diabetic patients. Recent evidence suggests that post-challenge hyperglycaemia is a better predictor of cardiovascular risk than fasting glucose. Acute glucose elevations have been associated with a reduced endothelial-dependent flow mediated dilation indicating a decrease in nitric oxide production. Post-prandial hyperglycaemic peaks have been directly associated with increased intima media thickness in type 2 diabetic patients indicative of an increased atherosclerotic risk.
The increase in intra-cellular glucose concentrations in the endothelial cells induces a hyper-generation of reactive oxygen species via the activation of different pathways (polyol-sorbitol, hexosamine, advanced glycated end products, activation of PKC, asymmetric dimethylarginine (ADMA)). These mechanisms influence the expression of genes and release of signalling and structural molecules involved in several functions (inflammation, angiogenesis, coagulation, vascular tone and permeability, cellular migration, nutrient metabolism).
ADMA is considered as a biomarker of endothelial dysfunction and it has been associated with an increased risk of atherosclerosis and cardiovascular diseases. The increased generation of ADMA and reactive oxygen species in subjects with persistent hyperglycaemia could lead to an impairment of nitric oxide synthesis.
| Item Type: | Journal Article |
|---|---|
| Subjects: | R Medicine > R Medicine (General) R Medicine > RB Pathology R Medicine > RC Internal medicine |
| Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Health Sciences Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
| Library of Congress Subject Headings (LCSH): | Insulin resistance, Nitric oxide, Nitric-oxide synthase -- Inhibitors, Inflammation, Oxidative stress |
| Journal or Publication Title: | Nutrition, Metabolism and Cardiovascular Diseases |
| Publisher: | Elsevier Ltd |
| ISSN: | 09394753 |
| Official Date: | January 2011 |
| Dates: | Date Event January 2011 Published |
| Volume: | Vol.21 |
| Number: | No.1 |
| Page Range: | pp. 1-10 |
| DOI: | 10.1016/j.numecd.2010.10.003 |
| Status: | Peer Reviewed |
| Publication Status: | Published |
| Access rights to Published version: | Restricted or Subscription Access |
| URI: | https://wrap.warwick.ac.uk/37382/ |
Data sourced from Thomson Reuters' Web of Knowledge
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