Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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3T3 Cells
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Adipocytes / metabolism
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Amino Acid Sequence
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Animals
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Base Sequence
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Chromosomes, Human, Pair 19
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Cloning, Molecular
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DNA
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Diabetes Mellitus / blood
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Diabetes Mellitus / etiology*
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Diabetes Mellitus / metabolism
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Diabetes Mellitus, Type 2 / blood
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Diabetes Mellitus, Type 2 / complications*
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Diabetes Mellitus, Type 2 / metabolism
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Diet
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Female
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Gene Expression Regulation / drug effects
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Glucose Intolerance
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Hormones / genetics
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Hormones / metabolism
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Hormones / physiology*
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Hormones, Ectopic / genetics
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Hormones, Ectopic / metabolism
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Hormones, Ectopic / physiology*
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Humans
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Hypoglycemic Agents / pharmacology
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Insulin Antagonists
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Insulin Resistance
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Intercellular Signaling Peptides and Proteins*
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Male
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Mice
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Mice, Inbred C57BL
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Molecular Sequence Data
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Nerve Growth Factor
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Neutralization Tests
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Obesity*
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Proteins*
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Resistin
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Rosiglitazone
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Signal Transduction
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Thiazoles / pharmacology
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Thiazolidinediones*
Substances
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Hormones
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Hormones, Ectopic
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Hypoglycemic Agents
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Insulin Antagonists
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Intercellular Signaling Peptides and Proteins
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Proteins
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RETN protein, human
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RETNLB protein, human
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Resistin
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Retn protein, mouse
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Retnla protein, mouse
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Thiazoles
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Thiazolidinediones
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Rosiglitazone
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DNA
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Nerve Growth Factor
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2,4-thiazolidinedione
Associated data
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GENBANK/AC008763
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GENBANK/AF323080
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GENBANK/AF323081