The hormone resistin links obesity to diabetes

被引:3667
作者
Steppan, CM
Bailey, ST
Bhat, S
Brown, EJ
Banerjee, RR
Wright, CM
Patel, HR
Ahima, RS
Lazar, MA [1 ]
机构
[1] Univ Penn, Sch Med, Dept Med, Div Endocrinol Diabet & Metab, Philadelphia, PA 19104 USA
[2] Univ Penn, Sch Med, Dept Genet, Div Endocrinol Diabet & Metab, Philadelphia, PA 19104 USA
[3] Univ Penn, Sch Med, Penn Diabet Ctr, Philadelphia, PA 19104 USA
关键词
D O I
10.1038/35053000
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:307 / 312
页数:6
相关论文
共 35 条
[1]   Role of leptin in the neuroendocrine response to fasting [J].
Ahima, RS ;
Prabakaran, D ;
Mantzoros, C ;
Qu, DQ ;
Lowell, B ;
MaratosFlier, E ;
Flier, JS .
NATURE, 1996, 382 (6588) :250-252
[2]   PPARγ is required for placental, cardiac, and adipose tissue development [J].
Barak, Y ;
Nelson, MC ;
Ong, ES ;
Jones, YZ ;
Ruiz-Lozano, P ;
Chien, KR ;
Koder, A ;
Evans, RM .
MOLECULAR CELL, 1999, 4 (04) :585-595
[3]   Dominant negative mutations in human PPARγ associated with severe insulin resistance, diabetes mellitus and hypertension [J].
Barroso, I ;
Gurnell, M ;
Crowley, VEF ;
Agostini, M ;
Schwabe, JW ;
Soos, MA ;
Maslen, GL ;
Williams, TDM ;
Lewis, H ;
Schafer, AJ ;
Chatterjee, VKK ;
O'Rahilly, S .
NATURE, 1999, 402 (6764) :880-883
[4]  
BODEN G, 1997, DIABETES, V46, P1
[5]   PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR (PPAR)-GAMMA - ADIPOSE-PREDOMINANT EXPRESSION AND INDUCTION EARLY IN ADIPOCYTE DIFFERENTIATION [J].
CHAWLA, A ;
SCHWARZ, EJ ;
DIMACULANGAN, DD ;
LAZAR, MA .
ENDOCRINOLOGY, 1994, 135 (02) :798-800
[6]   Leptin and the regulation of body weight in mammals [J].
Friedman, JM ;
Halaas, JL .
NATURE, 1998, 395 (6704) :763-770
[7]   Identification of wortmannin-sensitive targets in 3T3-L1 adipocytes - Dissociation of insulin-stimulated glucose uptake and GLUT4 translocation [J].
Hausdorff, SF ;
Fingar, DC ;
Morioka, K ;
Garza, LA ;
Whiteman, EL ;
Summers, SA ;
Birnbaum, MJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (35) :24677-24684
[8]   Thiazolidinediones [J].
Henry, RR .
ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA, 1997, 26 (03) :553-&
[9]   FIZZ1, a novel cysteine-rich secreted protein associated with pulmonary inflammation, defines a new gene family [J].
Holcomb, IN ;
Kabakoff, RC ;
Chan, B ;
Baker, TW ;
Gurney, A ;
Henzel, W ;
Nelson, C ;
Lowman, HB ;
Wright, BD ;
Skelton, NJ ;
Frantz, GD ;
Tumas, DB ;
Peale, FV ;
Shelton, DL ;
Hébert, CC .
EMBO JOURNAL, 2000, 19 (15) :4046-4055
[10]   The role of TNFα and TNF receptors in obesity and insulin resistance [J].
Hotamisligil, GS .
JOURNAL OF INTERNAL MEDICINE, 1999, 245 (06) :621-625