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Current Diabetes Reviews
ISSN (Print): 1573-3998
ISSN (Online): 1875-6417
VOLUME: 2
ISSUE: 1
DOI: 10.2174/157339906775473590









Insulin and Endothelial Function: Physiological Environment Defines Effect on Atherosclerotic Risk

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Author(s): Edward Duncan, Vivienne Ezzat and Mark Kearney
Pages 51-60 (10)
Abstract:
A number of population studies have suggested that hyperinsulinaemia is an independent risk factor for the development of cardiovascular atherosclerosis. Furthermore, there is an emerging body of evidence supporting a role for insulin as both a vasoregulatory and glucoregulatory peptide. Principal amongst insulins putative vascular effects is to stimulate release of the anti-atherosclerotic signalling molecule nitric oxide (NO) from endothelial cells. Moreover, there is data demonstrating that in parallel to insulin mediated glucose uptake, stimulation of NO release by insulin is blunted in insulin resistant conditions. A number of in-vitro studies have begun to dissect and define the pathway by which insulin stimulates release of NO from endothelial cells and complimentary studies in gene-modified murine models of abnormal insulin signalling and/or hyperinsulinaemia have begun to elucidate the role of hyperinsulinaemia in NO release in-vivo. It is emerging that the effects of insulin on endothelial function are complex and in part dependent on the physiological/pathophysiological environment present when insulin binds to its receptor on the endothelial cell surface. The present article reviews the evidence for insulin being a pro-atherosclerotic and anti-atherosclerotic peptide with particular reference to endothelial cell derived NO bioavailability. In the present review we attempt to clarify the complex relationship between insulin, endothelial function and the risk of atherosclerosis by using data from in-vivo and ex-vivo models.
Keywords:
Insulin, Endothelium, Hyperinsulinaemia, Nitric oxide
Affiliation:
Department of Cardiology, GKT School of Medicine, Kings College London, London, SE59PJ, UK.