Acceleration of Atherogenesis in Hyperinsulinemic Miniature Swine Animal Model

It has been well known that epidemiologically, there is clear correlation between insulin resistance and atherogenesis. Among several etiological factors for insulin resistance, hyperinsulinemia has been considered the major cause of the atherosclerosis. However, there has been no direct experimental evidence supportive of this hypothesis. In an attempt to prove such hypothesis, we have created a novel animal model for chronic hyperinsulinemia by means of the continuous insulin infusion (2u/kg body weight/day) into CSK miniature swine fed with a high cholesterol/high fat diet for 6 months. The serum insulin levels at fast in those animals were raised (ranging from 38.6 to 55.4μu/ml) and this hyperinsulinemia was maintained throughout the 6 months experiment. In this animal model, marked exacerbation of hypercholesterolemia (1348 vs. 883mg/dl) and atherosclerosis, especially coronary atherosclerosis were observed. These experimental data suggest that hyperinsulinemia may accelerate atherogenesis in hypercholesterolemic subjects. This animal model should also prove useful for further investigation of the mechanisms of atherosclerosis in hyperinsulinism.