Received June 22, 2007
Revised September 6, 2007
Accepted after revision September 21, 2007
Insulin resistance and endothelial cell dysfunction
Mark Kearney 1*,
Edward Duncan 2,
Matthew Kahn 1,
Stephen B Wheatcroft 1
1 University of Leeds
2 Kings College London
* To whom correspondence should be addressed. E-mail: m.t.kearney{at}leeds.ac.uk.
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Abstract |
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Type 2 diabetes and obesity are major risk factors for the development of cardiovascular atherosclerosis. Resistance to the metabolic effects of insulin on its traditional target tissues (muscle, liver and adipose tissue) is a central pathogenic feature of these disorders. However, the role of insulin resistance in non-canonical tissues such as the endothelium is less clear. Several large studies support a role for insulin resistance in the development of premature cardiovascular atherosclerosis independent of type 2 diabetes and obesity. A key step in the initiation and progression of atherosclerosis is a reduction in the bioactivity of endothelial cell derived nitric oxide (NO). NO is a signalling molecule which has a portfolio of potential anti-atherosclerotic effects. The presence of insulin receptors on endothelial cells is well documented and the endothelium has now emerged as a potentially important target tissue for insulin; with insulin stimulated production of NO a feature of insulins action on endothelial cells. The role of insulin resistance at the level of the endothelial cell in vascular pathophysiology is unclear. A number of studies in humans and gene-modified mice have demonstrated a close association between insulin resistance and NO bioactivity. In this review we discuss the link between insulin resistance and endothelial cell function in humans and demonstrate the complimentary information provided by murine models of obesity and insulin resistance in our understanding of the vasculopathy associated with type 2 diabetes and obesity.
Key Words:
Endothelium, Nitric oxide, Obesity
