Insulin and atherogenesis.
A number of processes are involved in the pathogenesis of atherosclerosis. These include an "injury" to the endothelial cell barrier of the inner lining of the artery, infiltration of the artery by lipid filled monocyte-macrophages, proliferation of smooth muscle cells, synthesis of connective tissue and thrombus formation. Insulin may be involved in several of these processes. Over 40 years ago it was shown that insulin is necessary for the production of experimental atherosclerosis in cholesterol fed, alloxan diabetic rabbits. Insulin inhibits regression and stimulates formation of lipid containing lesions in a number of species, and can promote lesions in animals fed normal diets. Insulin is also related to lipid metabolism in the artery wall and interacts with blood pressure to stimulate lipid synthesis in arteries. Arterial smooth muscle cells cultured from a number of species including humans proliferate in response to levels of insulin similar to those found in normal human physiology. The proliferative effects of insulin are mediated by the insulin-like growth factor receptor and hence may not be impaired in states of insulin resistance. Insulin also stimulates arterial smooth muscle cell migration. Insulin stimulates cholesterol synthesis in cultured smooth muscle cells and enhances LDL receptor activity in a number of cell types. Insulin stimulates connective tissue synthesis, and promotes clotting.
Stout
R W
RW
Department of Geriatric Medicine, Belfast.
D001158:Arteries / Q000378:metabolism* / Q000473:pathology; D001161:Arteriosclerosis / Q000209:etiology*; D002455:Cell Division / Q000502:physiology; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D006801:Humans; D006946:Hyperinsulinism / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D007328:Insulin / Q000502:physiology*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology; D011973:Receptors, LDL / Q000378:metabolism*
D007328:Insulin; D008077:Lipoproteins, LDL; D011973:Receptors, LDL