Hypertension, hypertriglyceridemia, and impaired endothelium-dependent vascular relaxation in mice lacking insulin receptor substrate-1

Insulin resistance is often associated with atherosclerotic diseases in subjects with obesity and impaired glucose tolerance, This study examined the effects of insulin resistance on coronary risk factors in IRS-1 deficient mice, a nonobese animal model of insulin resistance, Blood pressure and plasma triglyceride let els 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 to be involved in the increase in plasma triglyceride levels under insulin-resistant conditions, Thus, insulin resistance plays an important role in the clustering of coronary risk factors which may accelerate the progression of atherosclerosis in subjects with insulin resistance.