Insulin Signaling in Arteries Prevents Smooth Muscle Apoptosis

OBJECTIVE: Insulin is an antiapoptotic factor of cultured vascular cells, but it is not clear whether it also exerts antiapoptotic effects on vascular cells in vivo. We studied insulin receptor signaling in the arteries of normal and diabetic rats to establish whether insulin exhibits antiapoptotic activity toward vascular smooth muscle cells in vivo as well as in vitro. METHODS AND RESULTS: Western blot analysis and real-time polymerase chain reaction revealed alpha- and beta-subunits of the insulin receptor in association with insulin receptor substrate-1 and phosphatidylinositol 3-kinase in the media of the aorta and carotid artery. The insulin receptor signaling pathway was partially activated under physiological conditions, further activated by intravenous insulin injection, and was attenuated in streptozotocin-induced diabetic rats. Lipopolysaccharide injection induced more apoptosis of vascular smooth muscle cells in diabetic rats than in control rats, whereas insulin prevented apoptosis in the aortic wall. An in vitro study suggested that the antiapoptotic effect of insulin was mediated by phosphatidylinositol 3-kinase. CONCLUSIONS: Insulin is an antiapoptotic factor of vascular smooth muscle cells in vitro and in vivo. Decreased insulin activity on the artery may increase smooth muscle cell death and cause unstable plaque formation associated with diabetes.