Insulin Regulation of IGF-I Expression in Rat Aorta
- Departments of Internal Medicine, Physiology, and Pathology, Faculty of Medicine, University of Manitoba, Winnipeg Manitoba, Canada
- Address correspondence and reprint requests to Liam J. Murphy, MB, PhD, University of Manitoba, Department of Physiology, Room 435, Basic Science Building, 770 Bannatyne Avenue, Winnipeg, Manitoba R3E 0W3, Canada.
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.
- Received August 29, 1989.
- Revision received January 19, 1990.
- Accepted January 19, 1990.
- Copyright © 1990 by the American Diabetes Association