The hormone resistin links obesity to diabetes

• Published in: Nature (London) 2001-01, Vol.409 (6818), p.307-312
• Main Authors: Lazar, Mitchell A, Steppan, Claire M, Bailey, Shannon T, Bhat, Savitha, Brown, Elizabeth J, Banerjee, Ronadip R, Wright, Christopher M, Patel, Hiralben R, Ahima, Rexford S
• Format: Article
• Language: English
• Subjects: 3T3 Cells; Adipocytes - secretion; Amino Acid Sequence; Animals; Associated diseases and complications; Base Sequence; Biological and medical sciences; Cardiovascular diseases; Chromosomes, Human, Pair 19; Cloning, Molecular; Diabetes; diabetes mellitus; Diabetes Mellitus - blood; Diabetes Mellitus - etiology; Diabetes Mellitus - metabolism; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - metabolism; Diabetes. Impaired glucose tolerance; Diet; DNA; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Epidemics; Female; Gene Expression Regulation - drug effects; Glucose Intolerance; Hormones; Hormones - genetics; Hormones - metabolism; Hormones - physiology; Hormones - secretion; Hormones, Ectopic - genetics; Hormones, Ectopic - physiology; Hormones, Ectopic - secretion; Humanities and Social Sciences; Humans; Hypoglycemic Agents - pharmacology; Insulin Antagonists; Insulin Resistance; Intercellular Signaling Peptides and Proteins; Kidneys; Male; Medical research; Medical sciences; Mice; Mice, Inbred C57BL; Molecular Sequence Data; multidisciplinary; Nerve Growth Factor; Neutralization; Neutralization Tests; Obesity; Proteins; Resistin; Science; Science (multidisciplinary); Signal Transduction; Thiazoles - pharmacology; Thiazolidinediones
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/35053000

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.