Effect of thiazolidinediones and metformin on LDL oxidation and aortic endothelium relaxation in diabetic GK rats.
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.
Iida
Kaoruko Tada
KT
Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, Ibaraki 305-8575, Japan.
Kawakami
Yasushi
Y
Suzuki
Masatsune
M
Shimano
Hitoshi
H
Toyoshima
Hideo
H
Sone
Hirohito
H
Shimada
Kazunori
K
Iwama
Yoshitaka
Y
Watanabe
Yoshiro
Y
Mokuno
Hiroshi
H
Kamata
Katsuo
K
Yamada
Nobuhiro
N
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
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