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Am J Physiol Endocrinol Metab 284: E1125-E1130, 2003. First published February 4, 2003; doi:10.1152/ajpendo.00430.2002
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Vol. 284, Issue 6, E1125-E1130, June 2003

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

Kaoruko Tada Iida1, Yasushi Kawakami2, Masatsune Suzuki1, Hitoshi Shimano1, Hideo Toyoshima1, Hirohito Sone1, Kazunori Shimada3, Yoshitaka Iwama3, Yoshiro Watanabe3, Hiroshi Mokuno3, Katsuo Kamata4, and Nobuhiro Yamada1

1 Division of Endocrinology and Metabolism, Department of Internal Medicine, and 2 Department of Clinical Pathology, Institute of Clinical Medicine, University of Tsukuba, Ibaraki 305-8575; 3 Department of Cardiology, Juntendo University, Tokyo 113-8421; and 4 Departments of Physiology and Morphology, Institute of Medical Chemistry, Hoshi University, Tokyo 142-8501, Japan

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.

diabetes mellitus; low-density lipoprotein; endothelium; Goto-Kakizaki rats


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