Steppan C M, Bailey S T, Bhat S, Brown E J, Banerjee R R, Wright C M, Patel H R, Ahima R S, Lazar M A
Department of Medicine, The Penn Diabetes Center, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
Nature. 2001 Jan 18;409(6818):307-12. 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.
糖尿病是一种慢性疾病，可导致包括心脏病、中风、肾衰竭、失明和神经损伤在内的并发症。2型糖尿病以靶组织对胰岛素抵抗为特征，在工业化社会中流行，且与肥胖密切相关；然而，肥胖增加导致胰岛素抵抗的机制尚不清楚。在此我们表明，脂肪细胞分泌一种独特的信号分子，我们将其命名为抵抗素（resistin，取对胰岛素抵抗之意）。抗糖尿病药物罗格列酮可降低循环中的抵抗素水平，而在饮食诱导和基因导致的肥胖中抵抗素水平升高。给予抗抵抗素抗体可改善饮食诱导肥胖小鼠的血糖和胰岛素作用。此外，用重组抵抗素处理正常小鼠会损害葡萄糖耐量和胰岛素作用。通过中和抵抗素可增强脂肪细胞对胰岛素刺激的葡萄糖摄取，而抵抗素处理则会降低这种摄取。因此，抵抗素是一种可能将肥胖与糖尿病联系起来的激素。
