Chemerin regulates β-cell function in mice.

Chemerin regulates β-cell function in mice.
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DOI:
10.1038/srep00123
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发表时间:
2011
期刊:
影响因子:
4.6
通讯作者:
Takahashi, Yutaka
Takahashi, Yutaka
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Takahashi, Michiko;Okimura, Yasuhiko;Iguchi, Genzo;Nishizawa, Hitoshi;Yamamoto, Masaaki;Suda, Kentaro;Kitazawa, Riko;Fujimoto, Wakako;Takahashi, Kenichi;Zolotaryov, Fyodor N.;Hong, Kyoung Su;Kiyonari, Hiroshi;Abe, Takaya;Kaji, Hidesuke;Kitazawa, Sohei;Kasuga, Masato;Chihara, Kazuo;Takahashi, Yutaka

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虽然趋化素的多种功能已被提出,但其生理作用仍有待阐明。本研究表明,趋化素缺乏的小鼠是葡萄糖不耐受的,与脂肪组织中巨噬细胞积累减少无关。葡萄糖不耐受主要是由于肝脏葡萄糖生成增加和胰岛素分泌受损。Chemerin及其受体ChemR23在β-细胞中表达。使用离体胰岛和灌注胰腺的研究发现,趋化素缺乏小鼠的葡萄糖依赖性胰岛素分泌(GSIS)受损。相反,chemerin转基因小鼠显示GSIS增强和葡萄糖耐量改善。在趋化素缺乏的胰岛中,β细胞功能的关键转录因子MafA的表达下调,而在趋化素消融的β细胞系中,恢复MafA的表达可以恢复GSIS,这表明趋化素通过维持MafA的表达来调节β细胞功能。这些结果表明,趋化素调节β细胞功能,并以组织依赖的方式在葡萄糖稳态中发挥重要作用。
Although various function of chemerin have been suggested, its physiological role remains to be elucidated. Here we show that chemerin-deficient mice are glucose intolerant irrespective of exhibiting reduced macrophage accumulation in adipose tissue. The glucose intolerance was mainly due to increased hepatic glucose production and impaired insulin secretion. Chemerin and its receptor ChemR23 were expressed in β-cell. Studies using isolated islets and perfused pancreas revealed impaired glucose-dependent insulin secretion (GSIS) in chemerin-deficient mice. Conversely, chemerin transgenic mice revealed enhanced GSIS and improved glucose tolerance. Expression of MafA, a pivotal transcriptional factor for β-cell function, was downregulated in chemerin-deficient islets and a chemerin-ablated β-cell line and rescue of MafA expression restored GSIS, indicating that chemerin regulates β-cell function via maintaining MafA expression. These results indicate that chemerin regulates β-cell function and plays an important role in glucose homeostasis in a tissue-dependent manner.
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