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Diabetes 53:1937-1941, 2004
© 2004 by the American Diabetes Association, Inc.

Rapid Publication

Abnormal Glucose Homeostasis due to Chronic Hyperresistinemia

Shamina M. Rangwala1, A. Sophie Rich1, Ben Rhoades1, Jennifer S. Shapiro1, Silvana Obici2, Luciano Rossetti2, and Mitchell A. Lazar1

1 Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, The Penn Diabetes Center, Philadelphia, Pennsylvania
2 Department of Medicine, Diabetes Research and Training Center, Albert Einstein College of Medicine, Bronx, New York

Resistin is an adipocyte-secreted protein that circulates at increased levels in obesity. Acute administration of resistin impairs glucose tolerance, but the effects of chronic hyperresistinemia have not been established. Here we describe the generation and characterization of transgenic mice that have high circulating levels of resistin in the setting of normal weight. Fasted blood glucose was higher in resistin-transgenic mice than in their nontransgenic littermates, and glucose tolerance was impaired in the hyperresistinemic mice. Metabolic studies in the setting of a hyperinsulinemic-euglycemic clamp protocol revealed that chronically hyperresistinemic mice have elevated glucose production. This increase in glucose production may be partly explained by increased expression of hepatic phosphoenolpyruvate carboxykinase. Thus, chronic hyperresistinemia impairs normal glucose metabolism.

Address correspondence and reprint requests to Mitchell A. Lazar, MD, PhD, University of Pennsylvania School of Medicine, 611 CRB, 415 Curie Blvd., Philadelphia, PA 19104. E-mail: lazar{at}mail.med.upenn.edu


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