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Deletion of the Androgen Receptor in Adipose Tissue in Male Mice Elevates Retinol Binding Protein 4 and Reveals Independent Effects on Visceral Fat Mass and on Glucose Homeostasis

renchunxiao 添加于 2012/5/7 16:33:12  1126次阅读 | 0次推荐 | 0个评论

Testosterone deficiency is epidemic in obese ageing males with type 2 diabetes, but the direction of causality remains unclear. Testosterone-deficient males and global androgen receptor (AR) knockout mice are insulin resistant with increased fat, but it is unclear whether AR signaling in adipose tissue mediates body fat redistribution and alters glucose homoeostasis. To investigate this, mice with selective knockdown of AR in adipocytes (fARKO) were generated. Male fARKO mice on normal diet had reduced perigonadal fat but were hyperinsulinemic and by age 12 months, were insulin deficient in the absence of obesity. On high-fat diet, fARKO mice had impaired compensatory insulin secretion and hyperglycemia, with increased susceptibility to visceral obesity. Adipokine screening in fARKO mice revealed a selective increase in plasma and intra-adipose retinol binding protein 4 (RBP4) that preceded obesity. AR activation in murine 3T3 adipocytes downregulated RBP4 mRNA. We conclude that AR signaling in adipocytes not only protects against high-fat diet–induced visceral obesity but also regulates insulin action and glucose homeostasis, independently of adiposity. Androgen deficiency in adipocytes in mice resembles human type 2 diabetes, with early insulin resistance and evolving insulin deficiency.

作 者:Kerry J. McInnes1⇓, Lee B. Smith2, Nicole I. Hunger1, Philippa T.K. Saunders2, Ruth Andrew1 and Brian R. Walker1
期刊名称: diabets
期卷页: 第卷 第期 页
学科领域:生命科学 » 发育生物学与生殖生物学 » 生殖生物学
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原文链接:http://diabetes.diabetesjournals.org/content/61/5/1072.abstract?sid=0f438885-37a8-4211-806d-877fcb9936c8
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相关报道: http://paper.sciencenet.cn/htmlpaper/2012589464181524201.shtm
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