Insulin regulation of IGF-I expression in rat aorta.
Smooth muscle cell proliferation may be important in pathogenesis of atherosclerosis. Because insulinlike growth factor I (IGF-I) is a potent mitogen for arterial smooth muscle cells in culture, we examined the hypothesis that IGF-I functions as an autocrine growth factor in the aorta. We also investigated the role of insulin in regulation of IGF-I expression in the aorta. With immunohistochemical and in situ hybridization techniques, IGF-I immunoreactivity and IGF-I mRNA were localized to the smooth muscle layer of the aorta. In diabetic rats, aortic IGF-I mRNA abundance was significantly reduced to 60.3 +/- 2.9% of controls (P less than 0.01). In nondiabetic rats, administration of insulin as an acute bolus (10 U i.p.) or a chronic infusion (2.4 U/day for 5 days) resulted in an approximately twofold increase in abundance of IGF-I mRNA in the aorta. These observations are consistent with the hypothesis that IGF-I may function as an autocrine growth factor in the aorta and suggest that one of the mechanisms whereby hyperinsulinism may favor atherogenesis is enhanced expression of IGF-I in the vessel wall.
Murphy
L J
LJ
Department of Internal Medicine, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
Ghahary
A
A
Chakrabarti
S
S
D000818:Animals; D001011:Aorta / Q000378:metabolism*; D015152:Blotting, Northern; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D007150:Immunohistochemistry; D007328:Insulin / Q000494:pharmacology / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013002:Somatomedins / Q000378:metabolism*; D013311:Streptozocin; D014018:Tissue Distribution
D007328:Insulin; D012333:RNA, Messenger; D013002:Somatomedins; D013311:Streptozocin; D007334:Insulin-Like Growth Factor I