title: Effect of thiazolidinediones and metformin on LDL oxidation and aortic endothelium relaxation in diabetic GK rats.
abstract: In this study, using GK diabetic rats, we compared the effects of three insulin sensitizers on lipid oxidation and the aortic relaxation response. Eight-week-old rats were treated for 4 wk with either troglitazone or pioglitazone, both of which are thiazolidinediones, or with metformin. Despite the fact that only troglitazone has a similarity in structure to alpha-tocopherol, a potent antioxidant, the level of thiobarbituric acid-reactive substance was lower, and the lag time of the conjugated dienes was longer, in the blood samples from the rats in both troglitazone- and pioglitazone-treated groups. In contrast, another insulin sensitizer, metformin, failed to inhibit the oxidation of blood samples. The aortic vasorelaxation response was increased in both troglitazone- and metformin-treated groups compared with the untreated group. These findings suggest that thiazolidinediones have a beneficial effect on lipid oxidation irrespective of the drug's structural similarity to alpha-tocopherol. It is also suggested that the thiazolidinediones and metformin improve vascular function in diabetes. These effects may play a role in the prevention of atherosclerosis in diabetic patients.
authors.affiliation: Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Kaoruko Tada
authors.initials: KT
authors.lastname: Iida
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kawakami
authors.forename: Masatsune
authors.initials: M
authors.lastname: Suzuki
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Shimano
authors.forename: Hideo
authors.initials: H
authors.lastname: Toyoshima
authors.forename: Hirohito
authors.initials: H
authors.lastname: Sone
authors.forename: Kazunori
authors.initials: K
authors.lastname: Shimada
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Iwama
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mokuno
authors.forename: Katsuo
authors.initials: K
authors.lastname: Kamata
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Yamada
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001161:Arteriosclerosis / Q000473:pathology / Q000517:prevention & control; D008078:Cholesterol, LDL / Q000378:metabolism*; D002839:Chromans / Q000494:pharmacology; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007537:Isometric Contraction / Q000187:drug effects; D015227:Lipid Peroxidation; D008055:Lipids / Q000097:blood; D008297:Male; D008687:Metformin / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D010084:Oxidation-Reduction; D000077205:Pioglitazone; D051381:Rats; D017208:Rats, Wistar; D013844:Thiazoles / Q000494:pharmacology*; D045162:Thiazolidinediones; D000077288:Troglitazone; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D008078:Cholesterol, LDL; D002839:Chromans; D007004:Hypoglycemic Agents; D008055:Lipids; D013844:Thiazoles; D045162:Thiazolidinediones; D014665:Vasodilator Agents; D008687:Metformin; D000077288:Troglitazone; D000109:Acetylcholine; D000077205:Pioglitazone