The role of IGF-1 resistance in obesity and type 2 diabetes-mellitus-related insulin resistance and vascular disease.
BACKGROUND
The insulin-resistant conditions of type 2 diabetes mellitus (T2DM) and obesity are a major cause of cardiovascular disease on a global scale. These disorders are not only a cause of ill health but are a huge financial drain on healthcare systems. T2DM leads to an increased risk of cardiovascular mortality equivalent to over 10 years of ageing while obesity independent of T2DM also leads to a substantially increased risk of acute myocardial infarction. Recent trials of therapeutic agents and approaches to preventing the cardiovascular complications of type 2 diabetes have been disappointing.


METHODS
The role of insulin resistance in the endothelium in the regulation of the anti-atherosclerotic signalling molecule NO and a potential important role for IGF-1 in vascular NO production.


RESULTS
A comprehensive understanding of how insulin and IGF-1 regulate vascular function and the effect of type 2 diabetes on these pathways.


CONCLUSIONS
The roles of insulin and IGF-1 in vascular function are complex and intimately related. Nevertheless IGF-1 signalling in the arterial wall has the potential to be manipulated to protect the vasculature against the development of atherosclerosis and its devastating complications.
University of Leeds Multidisciplinary Cardiovascular Research Centre, Leeds, UK.
Victoria K
VK
Gatenby
Mark T
MT
Kearney
D000818:Animals; D050197:Atherosclerosis / Q000150:complications / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000150:complications / Q000188:drug therapy; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy; D004730:Endothelium, Vascular / Q000502:physiology; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000627:therapeutic use; D007333:Insulin Resistance; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D058990:Molecular Targeted Therapy; D009569:Nitric Oxide / Q000378:metabolism; D009765:Obesity / Q000150:complications / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D012307:Risk Factors; D016896:Treatment Outcome; D014652:Vascular Diseases / Q000150:complications / Q000188:drug therapy
D007004:Hypoglycemic Agents; D007328:Insulin; D009569:Nitric Oxide; D007334:Insulin-Like Growth Factor I