Published in Volume
101, Issue 8 (April 15,1998)
J. Clin. Invest.
101(8):
1784-1788 (1998).
doi:10.1172/JCI1594.
Copyright © 1998,
The American Society for Clinical Investigation
Research Article
Hypertension, hypertriglyceridemia, and impaired endothelium-dependent vascular relaxation in mice lacking insulin receptor substrate-1.
H Abe,
N Yamada,
K Kamata,
T Kuwaki,
M Shimada,
J Osuga,
F Shionoiri,
N Yahagi,
T Kadowaki,
H Tamemoto,
S Ishibashi,
Y Yazaki and
M Makuuchi
Second Department of Surgery, Faculty of Medicine, University of Tokyo, Tokyo, Japan.
Published April 15,
1998
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 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 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.
