title: Hypertension, hypertriglyceridemia, and impaired endothelium-dependent vascular relaxation in mice lacking insulin receptor substrate-1.
abstract: 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.
authors.affiliation: Second Department of Surgery, Faculty of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Abe
authors.forename: N
authors.initials: N
authors.lastname: Yamada
authors.forename: K
authors.initials: K
authors.lastname: Kamata
authors.forename: T
authors.initials: T
authors.lastname: Kuwaki
authors.forename: M
authors.initials: M
authors.lastname: Shimada
authors.forename: J
authors.initials: J
authors.lastname: Osuga
authors.forename: F
authors.initials: F
authors.lastname: Shionoiri
authors.forename: N
authors.initials: N
authors.lastname: Yahagi
authors.forename: T
authors.initials: T
authors.lastname: Kadowaki
authors.forename: H
authors.initials: H
authors.lastname: Tamemoto
authors.forename: S
authors.initials: S
authors.lastname: Ishibashi
authors.forename: Y
authors.initials: Y
authors.lastname: Yazaki
authors.forename: M
authors.initials: M
authors.lastname: Makuuchi
mesh_terms: 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*
chemical_list: D055504:Insulin Receptor Substrate Proteins; C526295:Irs1 protein, mouse; D008055:Lipids; D010750:Phosphoproteins; D011972:Receptor, Insulin