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1 Division of Endocrinology and Metabolism, Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, Tsukuba-shi, Ibaraki, Japan
2 Department of Clinical Pathology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba-shi, Ibaraki, Japan
3 Department of Cardiology, Juntendo University, Bunkyo-ku, Tokyo, Japan
4 Departments of Physiology and Morphology, Institute of Medical Chemistry, Hoshi University, Shinagawa-ku, Tokyo, Japan
* To whom correspondence should be addressed. E-mail: ymdnbhr{at}md.tsukuba.ac.jp.
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 either with troglitazone or pioglitazone, both of which are thiazolidinediones, or with metformin for 4-weeks. Despite the fact that only troglitazone has a similarity in structure with 
-tocopherol, a potent antioxidant, the levels of thiobarbituric acid reactive substance (TBARS) 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 drug-treated groups, compared with the untreated group. These findings suggest that thiazolidinediones have a beneficial effect on the lipid oxidation, irrespective of the drug's structural similarity to -tocopherol. It is also suggested that both thiazolidinediones and metformin improve vascular function in diabetes. These effects may play a role in the prevention of atherosclerosis in diabetic patients.
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