The hormone resistin links obesity to diabetes.
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.
Steppan
C M
CM
Department of Medicine, The Penn Diabetes Center, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
Bailey
S T
ST
Bhat
S
S
Brown
E J
EJ
Banerjee
R R
RR
Wright
C M
CM
Patel
H R
HR
Ahima
R S
RS
Lazar
M A
MA
D016475:3T3 Cells; D017667:Adipocytes / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002888:Chromosomes, Human, Pair 19; D003001:Cloning, Molecular; D004247:DNA; D003920:Diabetes Mellitus / Q000097:blood / Q000209:etiology* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications* / Q000378:metabolism; D004032:Diet; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D018149:Glucose Intolerance; D006728:Hormones / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006729:Hormones, Ectopic / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007329:Insulin Antagonists; D007333:Insulin Resistance; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D020932:Nerve Growth Factor; D009500:Neutralization Tests; D009765:Obesity; D011506:Proteins; D052243:Resistin; D000077154:Rosiglitazone; D015398:Signal Transduction; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones
D006728:Hormones; D006729:Hormones, Ectopic; D007004:Hypoglycemic Agents; D007329:Insulin Antagonists; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; C499624:RETN protein, human; C486574:RETNLB protein, human; D052243:Resistin; C499623:Retn protein, mouse; C413576:Retnla protein, mouse; D013844:Thiazoles; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D004247:DNA; D020932:Nerve Growth Factor; C089946:2,4-thiazolidinedione