Insulin signaling in the arterial wall.
Insulin has several direct vascular actions that contribute to either vascular protection or injury, depending on the cell type. Vascular protective effects of insulin include stimulation of endothelial cell production of the vasodilator nitric oxide (NO). This, in turn, inhibits formation of lesions dependent on migration and proliferation of vascular smooth muscle cells (VSMCs), attenuates binding of inflammatory cells to the vascular wall, and inhibits thrombosis by reducing platelet adhesion and aggregation. However, insulin also promotes a host of deleterious vascular effects by stimulating the actions of various growth factors acting through the mitogen-activated protein kinase (MAPK) signaling pathway. MAPK may mediate the effects of insulin and angiotensin II on VSMC production of plasminogen activator inhibitor-1, which attenuates fibrinolysis. Thus, 1 of the 2 major pathways of insulin action is the phosphatidylinositol 3-kinase pathway, which is important for glucose transport in skeletal muscle, as well as endothelial NO production and insulin-induced vasodilation. The second insulin-activated pathway is the MAPK pathway, which promotes VSMC growth factors and migration induced by insulin, thrombin, angiotensin II, and platelet-derived growth factor. The thiazolidinediones, which act as ligands for peroxisomal proliferator-activated receptor gamma, may inhibit VSMC growth and migration through inhibition of a variety of transcription factors involved in the MAPK pathway.
Department of Medicine, University of California Los Angeles School of Medicine, USA.
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D000818:Animals; D001158:Arteries / Q000378:metabolism / Q000503:physiopathology*; D002465:Cell Movement / Q000502:physiology; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000378:metabolism / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism / Q000502:physiology*; D007333:Insulin Resistance / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D013844:Thiazoles / Q000378:metabolism / Q000494:pharmacology; D045162:Thiazolidinediones
D007004:Hypoglycemic Agents; D007328:Insulin; D013844:Thiazoles; D045162:Thiazolidinediones; C089946:2,4-thiazolidinedione