Insulin glargine reduces carotid intimal hyperplasia after balloon catheter injury in Zucker fatty rats possibly by reduction in oxidative stress

Diabetes and impaired glucose tolerance are associated with increased cardiovascular disease morbidity and mortality particularly after vascular injury. Since insulin is frequently used in such patients, the effect of glulisine (short acting) and glargine (long acting) were tested in Zucker fatty rat carotid artery subjected to balloon catheter injury. Insulin-resistant Zucker fatty rats were sc injected 0.45 mg/kg/d of glargine (once) or glulisine (twice) for 1 week before, and 3 weeks after balloon injury. Fasting and postprandial glucose was measured twice weekly. Injured and uninjured carotid arteries, liver, and aorta were harvested after 3 weeks of injury. Carotid sections were H&E stained for measuring intima/media ratio or immunostained for nitrotyrosine. Serum and aortic protein were analyzed for IGF-1 and 8-isoprostane, respectively. Carotid intima/media ratio was significantly reduced in the glargine group [0.9 ± 0.1—control; 0.6 ± 0.1—glulisine; 0.4 ± 0.1—glargine, P < 0.05]. Serum IGF-1 levels were higher in both insulins, but significant only in glargine group [567 ± 121 (ng/ml)—control; 1059 ± 150 (ng/ml)—glargine; P < 0.05]. The aortic 8-isoprostane levels decreased significantly in the glargine group [(921 vs. 2566 pg/mg protein; P < 0.05]. Compared to control nitrotyrosine staining intensity was significantly lower in both groups of insulin-treated rats; the lowest level was in the glargine group. Insulin glargine attenuates carotid intimal hyperplasia in nondiabetic Zucker fatty rat independent of glucose levels and support a valuable function for insulin in vascular disease that merits additional investigations.