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 < 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.

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