Animal models for hyperinsulinemia and insulin resistance.

The direct effect of endogenous insulin on the atherosclerotic process has not been well understood. To clarify this question, we performed pancreas transplantation in Wistar Shionogi (WS) rats. Hyperinsulinemia was not related to coronary risk factors such as dyslipidemia and hypertension in transplanted rats. After 9 months of transplantation, the cholesterol ester contents of the aortas of transplanted WS rats were significantly higher than in the control rats. The effects of insulin resistance on coronary risk factors were examined in mice deficient in insulin substrate-1-deficient (IRS-1) mice, a non-obese animal model of insulin resistance. Blood pressure and plasma triglyceride levels were significantly higher in IRS-1-deficient mice than in normal mice. Impaired endothelium-dependent vascular relaxation was also observed in IRS-1-deficient mice. Furthermore, lipoprotein lipase activity was lower than in normal mice, suggesting impaired lipolysis was involved in the increased plasma triglyceride levels under insulin-resistant conditions.