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Nature 409, 307-312 (18 January 2001) | doi:10.1038/35053000; Received 9 June 2000; Accepted 15 November 2000

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The hormone resistin links obesity to diabetes

Claire M. Steppan, Shannon T. Bailey, Savitha Bhat, Elizabeth J. Brown, Ronadip R. Banerjee, Christopher M. Wright, Hiralben R. Patel, Rexford S. Ahima & Mitchell A. Lazar

  1. Division of Endocrinology, Diabetes, and Metabolism, Departments of Medicine and Genetics, and The Penn Diabetes Center, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA

Correspondence to: Mitchell A. Lazar Correspondence and requests for materials should be addressed to M.A.L.
(e-mail: Email: lazar@mail.med.upenn.edu).
The mouse and human resistin proteins are deposited under GenBank accession numbers AF323080 and AF323081, respectively.

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Diabetes mellitus is a chronic disease that leads to complications including heart disease, stroke, kidney failure, blindness and nerve damage. Type 2 diabetes, characterized by target-tissue resistance to insulin, is epidemic in industrialized societies and is strongly associated with obesity; however, the mechanism by which increased adiposity causes insulin resistance is unclear. Here we show that adipocytes secrete a unique signalling molecule, which we have named resistin (for resistance to insulin). Circulating resistin levels are decreased by the anti-diabetic drug rosiglitazone, and increased in diet-induced and genetic forms of obesity. Administration of anti-resistin antibody improves blood sugar and insulin action in mice with diet-induced obesity. Moreover, treatment of normal mice with recombinant resistin impairs glucose tolerance and insulin action. Insulin-stimulated glucose uptake by adipocytes is enhanced by neutralization of resistin and is reduced by resistin treatment. Resistin is thus a hormone that potentially links obesity to diabetes.

  1. Division of Endocrinology, Diabetes, and Metabolism, Departments of Medicine and Genetics, and The Penn Diabetes Center, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA

Correspondence to: Mitchell A. Lazar Correspondence and requests for materials should be addressed to M.A.L.
(e-mail: Email: lazar@mail.med.upenn.edu).
The mouse and human resistin proteins are deposited under GenBank accession numbers AF323080 and AF323081, respectively.