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 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.
Abe
H
H
Second Department of Surgery, Faculty of Medicine, University of Tokyo, Tokyo, Japan.
Yamada
N
N
Kamata
K
K
Kuwaki
T
T
Shimada
M
M
Osuga
J
J
Shionoiri
F
F
Yahagi
N
N
Kadowaki
T
T
Tamemoto
H
H
Ishibashi
S
S
Yazaki
Y
Y
Makuuchi
M
M
D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology; D001794:Blood Pressure / Q000235:genetics / Q000502:physiology; D004730:Endothelium, Vascular / Q000503:physiopathology; D005260:Female; D006973:Hypertension / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D015228:Hypertriglyceridemia / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D066298:In Vitro Techniques; D055504:Insulin Receptor Substrate Proteins; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology; D008055:Lipids / Q000097:blood; D051379:Mice; D018345:Mice, Knockout; D010750:Phosphoproteins / Q000172:deficiency* / Q000235:genetics; D011972:Receptor, Insulin / Q000378:metabolism*; D012307:Risk Factors; D014664:Vasodilation / Q000235:genetics / Q000502:physiology*
D055504:Insulin Receptor Substrate Proteins; C526295:Irs1 protein, mouse; D008055:Lipids; D010750:Phosphoproteins; D011972:Receptor, Insulin