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1 First Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan
* To whom correspondence should be addressed. E-mail: hirano{at}med.showa-u.ac.jp.
The effects of angiotensin II type 1 receptor blocker (ARB) on triglyceride (TG) metabolism associated with insulin resistance were explored in Zucker fatty (ZF) rats. Olmesartan Medoxiomil, a newly developed ARB, was given as a 0.01% drinking solution ad. libitum to ZF and Zucker lean (ZL) rats for 4 weeks. Olmesartan lowered blood pressure in both strains to the same extent. ZF rats had markedly low insulin sensitivity index (SI) and glucose effectiveness (SG) together with significantly increased glucose levels. Olmesartan treatment substantially elevated both SI and SG. The ZF rats were hyperlipidemic, with plasma TG levels 6-fold higher than those of the ZL rats. Olmesartan remarkably decreased the plasma free fatty acid level in the ZF, but it did not exert a significant effect on the plasma TG level. The TG secretion rate assessed by the Triton WR-1339 technique was almost 6 times higher in the ZF than in the ZL, and olmesartan treatment suppressed this TG overproduction by half. The TG content in the liver was ten-times higher in the ZF than in the ZL, and olmesartan halved this high hepatic TG content without affecting the cholesterol content. The fatty liver developed in the ZF rats were ameliorated by olmesartan treatment. Olmesartan treatment had no significant effects on TG metabolism or insulin sensitivity in the ZL rats. Taken in sum, ARB improves the overproduction and accumulation of TG in the liver associated with insulin resistance, and does so through mechanisms independent of its hypotensive action.
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