美国研究人员日前报告说，去除实验鼠体内的一种关键调控蛋白，可显著提高其对胰岛素的敏感性。这项研究为糖尿病治疗和药物研发提供了新途径。
美国加州大学圣迭戈分校的研究人员在美国《细胞》（Cell）杂志网站上报告说，他们培育了体内脂肪细胞缺少核受体辅助抑制因子的小鼠，然后用促使小鼠肥胖并易患上糖尿病的食物喂养。研究人员发现，这类小鼠对血糖升高的耐受性有显著提高，其肝脏、肌肉和脂肪对胰岛素的敏感性得到改善，体内的系统性炎症也有所减少。
胰岛素抵抗与慢性系统性炎症是Ⅱ型糖尿病的重要特征。胰岛素抵抗是指机体对胰岛素的敏感性降低，其利用胰岛素促进葡萄糖代谢的能力下降。
研究人员表示，核受体辅助抑制因子似乎能促进一种调节脂肪酸存储和血糖代谢的常见蛋白质PPAR－γ磷酸化，进而使这种蛋白质失去活性。去除小鼠的核受体辅助抑制因子后，PPAR－γ蛋白质就能保持活性，因而可以继续改善血糖代谢。
研究人员说，这意味着核受体辅助抑制因子可能是较好的Ⅱ型糖尿病药物靶点。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
