Role of insulin resistance and hyperglycemia in the development of atherosclerosis.
Insulin resistance (IR) is the underlying defect in >90% of patients with type 2 diabetes mellitus and the major pathologic mechanism for the associated susceptibility to premature cardiovascular disease (CVD). The progression of IR to diabetes parallels the progression of endothelial dysfunction to atherosclerosis. The downregulation of the antiatherogenic phosphatidylinositol-3-kinase-mediated insulin receptor-signaling pathway, and maintained activity of the proatherogenic mitogenic-activated protein kinase pathway in insulin-resistant states, leads to accelerated atherosclerosis. Efforts to prevent or slow the epidemic of atherothrombotic CVD must focus on the reversal of the disturbances in glucose and lipid homeostasis through the amelioration of IR.
Bansilal
Sameer
S
The Zena and Michael A. Wiener Cardiovascular Institute and The Marie-Josee and Henry R. Kravis Cardiovascular Health Center, Mount Sinai School of Medicine, New York, New York 10029-6574, USA.
Farkouh
Michael E
ME
Fuster
Valentin
V
D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D003324:Coronary Artery Disease / Q000378:metabolism / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism / Q000503:physiopathology*; D007333:Insulin Resistance / Q000502:physiology*; D009000:Monocytes / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D011972:Receptor, Insulin / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism
D011972:Receptor, Insulin