美國研究人員日前報告說，去除實驗鼠體內(nèi)的一種關(guān)鍵調(diào)控蛋白,，可顯著提高其對胰島素的敏感性,。這項研究為糖尿病治療和藥物研發(fā)提供了新途徑,。
美國加州大學(xué)圣迭戈分校的研究人員在美國《細胞》（Cell）雜志網(wǎng)站上報告說,，他們培育了體內(nèi)脂肪細胞缺少核受體輔助抑制因子的小鼠，然后用促使小鼠肥胖并易患上糖尿病的食物喂養(yǎng),。研究人員發(fā)現(xiàn),，這類小鼠對血糖升高的耐受性有顯著提高，其肝臟,、肌肉和脂肪對胰島素的敏感性得到改善,，體內(nèi)的系統(tǒng)性炎癥也有所減少。
胰島素抵抗與慢性系統(tǒng)性炎癥是Ⅱ型糖尿病的重要特征,。胰島素抵抗是指機體對胰島素的敏感性降低,，其利用胰島素促進葡萄糖代謝的能力下降。
研究人員表示,，核受體輔助抑制因子似乎能促進一種調(diào)節(jié)脂肪酸存儲和血糖代謝的常見蛋白質(zhì)PPAR－γ磷酸化,，進而使這種蛋白質(zhì)失去活性。去除小鼠的核受體輔助抑制因子后,，PPAR－γ蛋白質(zhì)就能保持活性,，因而可以繼續(xù)改善血糖代謝。
研究人員說,，這意味著核受體輔助抑制因子可能是較好的Ⅱ型糖尿病藥物靶點,。生物谷Bioon.com）
doi:10.1016/j.cell.2011.09.050
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Adipocyte NCoR Knockout Decreases PPAR Phosphorylation and Enhances PPAR Activity and Insulin Sensitivity
Pingping Li, WuQiang Fan, Jianfeng Xu, Min Lu, Hiroyasu Yamamoto, Johan Auwerx, Dorothy D. Sears, Saswata Talukdar, DaYoung Oh, Ai Chen, Gautam Bandyopadhyay, Miriam Scadeng, Jachelle M. Ofrecio, Sarah Nalbandian, Jerrold M. Olefsky
Insulin resistance, tissue inflammation, and adipose tissue dysfunction are features of obesity and Type 2 diabetes. We generated adipocyte-specific Nuclear Receptor Corepressor (NCoR) knockout (AKO) mice to investigate the function of NCoR in adipocyte biology, glucose and insulin homeostasis. Despite increased obesity, glucose tolerance was improved in AKO mice, and clamp studies demonstrated enhanced insulin sensitivity in liver, muscle, and fat. Adipose tissue macrophage infiltration and inflammation were also decreased. PPAR response genes were upregulated in adipose tissue from AKO mice and CDK5-mediated PPAR ser-273 phosphorylation was reduced, creating a constitutively active PPAR state. This identifies NCoR as an adaptor protein that enhances the ability of CDK5 to associate with and phosphorylate PPAR . The dominant function of adipocyte NCoR is to transrepress PPAR and promote PPAR ser-273 phosphorylation, such that NCoR deletion leads to adipogenesis, reduced inflammation, and enhanced systemic insulin sensitivity, phenocopying the TZD-treated state
