The Effect of Insulin on Atherosclerosis and Restenosis

Diabetes mellitus and metabolic syndrome, which are states of insulin resistance, are both well-known to increase the risk of atherosclerosis and restenosis. We present evidence that insulin itself is anti-atherogenic and anti-restenotic. Systemic insulin treatment decreases atherosclerosis independent of its effects on glycemia. Insulin-treated ApoE -/- mice showed a 42% decrease in plaque burden in the descending aorta and an increase in markers of plaque stability in the aortic sinus. We have previously shown that systemic insulin treatment decreases neointima area after arterial injury. However, systemic insulin treatment has the risk of hypoglycemia. Therefore we explored an alternative local route of application of insulin around the vessel via Pluronic gel in rats. We found that regular insulin and neutral protamine Hagedorn (NPH) insulin significantly decrease neointima area by 24% and 17% respectively at 28 days. These studies suggest that insulin is vasculoprotective.MAS