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Diabetes 56:239-247, 2007
DOI: 10.2337/db06-0353
© 2007 by the American Diabetes Association
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Prevention and Treatment of Obesity, Insulin Resistance, and Diabetes by Bile Acid–Binding Resin

Misato Kobayashi1, Hiroshi Ikegami1,2, Tomomi Fujisawa1, Koji Nojima1, Yumiko Kawabata1,2, Shinsuke Noso1, Naru Babaya1, Michiko Itoi-Babaya1, Kaori Yamaji1, Yoshihisa Hiromine1, Masao Shibata3, and Toshio Ogihara1

1 Department of Geriatric Medicine, Osaka University Graduate School of Medicine, Suita, Japan
2 Department of Endocrinology, Metabolism and Diabetes, Kinki University School of Medicine, Osaka-Sayama, Japan
3 College of General Education, Aichi-Gakuin University, Nishin, Japan

Address correspondence and reprint requests to Hiroshi Ikegami, Department of Endocrinology, Metabolism and Diabetes, Kinki University School of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka 589-8511, Japan. E-mail: ikegami{at}med.kindai.ac.jp

Abbreviations: BAT, brown adipose tissue; CPT-1, carnitine palmitoyltransferase 1; FAS, fatty acid synthase; LXR, liver X receptor; SHP, small heterodimer partner

Bile acid–binding resins, such as cholestyramine and colestimide, have been clinically used as cholesterol-lowering agents. These agents bind bile acids in the intestine and reduce enterohepatic circulation of bile acids, leading to accelerated conversion of cholesterol to bile acids. A significant improvement in glycemic control was reported in patients with type 2 diabetes whose hyperlipidemia was treated with bile acid–binding resins. To confirm the effect of such drugs on glucose metabolism and to investigate the underlying mechanisms, an animal model of type 2 diabetes was given a high-fat diet with and without colestimide. Diet-induced obesity and fatty liver were markedly ameliorated by colestimide without decreasing the food intake. Hyperglycemia, insulin resistance, and insulin response to glucose, as well as dyslipidemia, were markedly and significantly ameliorated by the treatment. Gene expression of the liver indicated reduced expression of small heterodimer partner, a pleiotropic regulator of diverse metabolic pathways, as well as genes for both fatty acid synthesis and gluconeogenesis, by treatment with colestimide. This study provides a molecular basis for a link between bile acids and glucose metabolism and suggests the bile acid metabolism pathway as a novel therapeutic target for the treatment of obesity, insulin resistance, and type 2 diabetes.


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Copyright © 2007 by the American Diabetes Association.