Insulin resistance, lipotoxicity and endothelial dysfunction.
The number of people with the insulin-resistant conditions of type 2 diabetes mellitus (T2DM) and obesity has reached epidemic proportions worldwide. Eighty percent of people with T2DM will die from the complications of cardiovascular atherosclerosis. Insulin resistance is characterised by endothelial dysfunction, which is a pivotal step in the initiation/progression of atherosclerosis. A hallmark of endothelial dysfunction is an unfavourable imbalance between the bioavailability of the antiatherosclerotic signalling molecule nitric oxide (NO) and proatherosclerotic reactive oxygen species. In this review we discuss the mechanisms linking insulin resistance to endothelial dysfunction, with a particular emphasis on a potential role for a toxic effect of free fatty acids on endothelial cell homeostasis.
Imrie
Helen
H
Division of Cardiovascular and Diabetes Research, Leeds Multidisciplinary Cardiovascular Research Centre, The LIGHT Laboratories, Clarendon Way, Leeds, LS29JT, UK. h.imrie@leeds.ac.uk
Abbas
Afroze
A
Kearney
Mark
M
D000818:Animals; D050171:Dyslipidemias / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D006801:Humans; D007333:Insulin Resistance; D019255:NADPH Oxidases / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D014652:Vascular Diseases / Q000378:metabolism*
D005230:Fatty Acids, Nonesterified; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D019255:NADPH Oxidases