來(lái)自美國(guó)加州大學(xué)圣地亞哥分校醫(yī)學(xué)院的研究人員說(shuō)，數(shù)量豐富的一類(lèi)白細(xì)胞,，即嗜中性粒細(xì)胞(neutrophil),，通常起著攻擊細(xì)菌和其他外來(lái)入侵物的作用，然而它們也在調(diào)控胰島素耐受性上也發(fā)揮著一種令人意想不到的作用,，其中胰島素耐受性是II型糖尿病的主要特征,。2012年8月5日，這些研究發(fā)現(xiàn)在線發(fā)表在Nature Medicine期刊上,。
嗜中性粒細(xì)胞是首批對(duì)組織炎癥作出反應(yīng)的免疫細(xì)胞,，能夠通過(guò)招募巨噬細(xì)胞來(lái)促進(jìn)慢性炎癥產(chǎn)生。慢性低度炎癥(chronic low-grade inflammation)在脂肪組織中比較常見(jiàn),，是一種產(chǎn)生系統(tǒng)性胰島素耐受性的重要原因,。
利用小鼠和人類(lèi)肝細(xì)胞以及活的小鼠模式動(dòng)物，加州大學(xué)圣地亞哥分校醫(yī)學(xué)教授Jerrold M. Olefsky博士領(lǐng)導(dǎo)的一個(gè)研究小組發(fā)現(xiàn)嗜中性粒細(xì)胞分泌出的一種酶,，即嗜中性粒細(xì)胞彈性蛋白酶(neutrophil elastase, NE),，損害胰島素信號(hào)通路，從而促進(jìn)胰島素耐受性產(chǎn)生,。相反地,，剔喂食高脂肪食物的肥胖小鼠中的NE，能夠改善小鼠對(duì)胰島素的敏感性,。
特別地,，嗜中性粒細(xì)胞利用NE來(lái)激活一種觸發(fā)吞噬病原體的巨噬細(xì)胞分泌促炎癥分子(proinflammatory molecule)的信號(hào)通路。NE降解一種在肝細(xì)胞和脂肪細(xì)胞胰島素信號(hào)通路中發(fā)揮關(guān)鍵性作用的蛋白IRS1,。盡管已知NE在肺癌細(xì)胞中降解這種蛋白,，但是它對(duì)諸如肝臟和脂肪組織之類(lèi)的胰島素靶組織的影響是十分顯著的。嗜中性粒細(xì)胞調(diào)節(jié)胰島素的作用使得它們成為一種新的靶標(biāo),，從而能夠被用來(lái)開(kāi)發(fā)出新的治療方法來(lái)治療胰島素耐受性和糖尿病,。(生物谷：Bioon.com)
本文編譯自Neutrophils: White blood cells mediate insulin resistance
doi: 10.1038/nm.2885
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PMID:
Neutrophils mediate insulin resistance in mice fed a high-fat diet through secreted elastase
Saswata Talukdar, Da Young Oh, Gautam Bandyopadhyay, Dongmei Li, Jianfeng Xu, Joanne McNelis, Min Lu, Pingping Li, Qingyun Yan, Yimin Zhu, Jachelle Ofrecio, Michael Lin, Martin B Brenner & Jerrold M Olefsky
Chronic low-grade adipose tissue and liver inflammation is a major cause of systemic insulin resistance and is a key component of the low degree of insulin sensitivity that exists in obesity and type 2 diabetes1, 2. Immune cells, such as macrophages, T cells, B cells, mast cells and eosinophils, have all been implicated as having a role in this process3, 4, 5, 6, 7, 8. Neutrophils are typically the first immune cells to respond to inflammation and can exacerbate the chronic inflammatory state by helping to recruit macrophages and by interacting with antigen-presenting cells9, 10, 11. Neutrophils secrete several proteases, one of which is neutrophil elastase, which can promote inflammatory responses in several disease models12. Here we show that treatment of hepatocytes with neutrophil elastase causes cellular insulin resistance and that deletion of neutrophil elastase in high-fat-diet–induced obese (DIO) mice leads to less tissue inflammation that is associated with lower adipose tissue neutrophil and macrophage content. These changes are accompanied by improved glucose tolerance and increased insulin sensitivity. Taken together, we show that neutrophils can be added to the extensive repertoire of immune cells that participate in inflammation-induced metabolic disease.
