Insulin and insulin-like growth factor I differentially induce α1- adrenergic receptor subtype expression in rat vascular smooth muscle cells

Abstract

Hyperinsulinemia has been implicated as an important risk factor for the development of accelerated cardiovascular disease. We wondered if insulin or IGF-I induced expression of α1 adrenergic receptors in vascular smooth muscle cells (VSMCs) which could enhance smooth muscle contraction and cell growth activated by catecholamines. Rat aortic VSMCs were incubated with insulin or IGF-I for various times and expression of α1 receptors was detected using [3H]prazosin binding. Both insulin and IGF-I increased α1 receptor number; also, these peptides increased expression of the α(1D) receptor gene with no change in expression of the α(1B) receptor gene as detected by RNase protection assays. Using Western blotting, we found that these peptides increased expression of the α(1D) receptor subtype in these cells. Increased expression of the α(1D) receptor mRNA was inhibited by the receptor tyrosine kinase inhibitor genistein and the PI 3-kinase inhibitor wortmannin but was not inhibited by protein kinase C inhibitor H7 or the L- type calcium channel blocker nifedipine. Preincubation of cells with insulin or IGF-I enhanced subsequent norepinephrine stimulation of mitogen activated kinase activity. These results suggest that insulin/IGF-I regulate expression of α1 receptors in VSMCs and potentially enhance the effects of catecholamines in settings of hyperinsulinemia.