Effect of thiazolidinediones and metformin on LDL oxidation and aortic endothelium relaxation in diabetic GK rats

American Journal of Physiology - Endocrinology and Metabolism - Tập 284 Số 6 - Trang E1125-E1130 - 2003
Kaoruko Iida1, Yasushi Kawakami2, Masatsune Suzuki1, Hitoshi Shimano1, Hideo Toyoshima1, Hirohito Sone1, Kazunori Shimada3, Yoshitaka Iwama3, Yoshirô Watanabe3, Hiroshi Mokuno3, Katsuo Kamata4, Nobuhiro Yamada1
1Division of Endocrinology and Metabolism, Department of Internal Medicine, and
2Department of Clinical Pathology, Institute of Clinical Medicine, University of Tsukuba, Ibaraki 305-8575;
3Department of Cardiology, Juntendo University, Tokyo 113-8421; and
4Departments of Physiology and Morphology, Institute of Medical Chemistry, Hoshi University, Tokyo 142-8501, Japan

Tóm tắt

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 α-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 α-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.

Từ khóa


Tài liệu tham khảo

10.1172/JCI1594

10.7326/0003-4819-131-3-199908030-00004

10.1056/NEJM199602293340906

10.1152/ajpendo.1993.265.5.E807

10.1161/01.ATV.21.3.372

10.1007/s001250050809

10.1111/j.1476-5381.1988.tb11548.x

10.2337/diab.37.11.1549

Ikeda H, 1990, Arzneimittelforschung, 40, 156

10.1006/bbrc.1997.6512

10.1007/BF00254833

10.1038/344160a0

10.1074/jbc.270.22.12953

10.1146/annurev.med.52.1.239

10.1016/S0014-2999(01)00866-4

10.1016/0021-9150(96)05811-X

10.1016/S1056-8727(97)00053-6

10.2337/diab.40.4.486

10.1002/dmr.5610030206

10.2337/diab.37.12.1595

10.2337/diab.45.12.1661

10.2337/diabetes.49.12.2178

10.1042/bj2960329

10.1172/JCI114718

10.1111/j.1749-6632.1990.tb42284.x

10.1056/NEJM199508313330903

10.1016/S0026-0495(99)90226-3

10.1016/S0140-6736(98)07037-8

10.1016/0006-2944(76)90049-1

10.2337/diacare.17.2.107