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Papers In Press, published online ahead of print May 24, 2002
J. Biol. Chem, 10.1074/jbc.C200251200
Submitted on April 24, 2002
Revised on May 16, 2002
Accepted on May 23, 2002
Department of Metabolic Diseases, University of Tokyo, Tokyo 113-8655
Corresponding Author: kadowaki-3im{at}h.u-tokyo.ac.jp
The adipocyte-derived hormone adiponectin has been proposed to play important roles in the regulation of energy homeostasis and insulin sensitivity, and it has been reported to exhibit putative anti-atherogenic properties in vitro. In this study we generated adiponectin-deficient mice to directly investigate whether adiponectin has a physiological protective role against diabetes and atherosclerosis in vivo. Heterozygous adiponectin-deficient (adipo+/-) mice showed mild insulin resistance, while homozygous adiponectin-deficient (adipo-/-) mice showed moderate insulin resistance with mild glucose intolerance despite body weight gain similar to that of wild-type mice. Moreover, adipo-/- mice showed 2 fold more neointimal formation in response to external vascular cuff injury than wild-type mice (P=0.01). This study provides the first direct evidence that adiponectin plays a protective role against insulin resistance and atherosclerosis in vivo.
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