Cell子刊：击败疯狂免疫细胞根治糖尿病

　　

生物通报道，美国加州大学医学院内分泌学与代谢学院Jaap G. Neels研究小组发现一种巧妙的糖尿病治疗手段，通过杀死过度活跃的免疫细胞消除肥胖机体脂肪组织和肌肉组织对胰岛素的耐受性，可降低血糖治疗糖尿病。相关结果公布在10月8日《Cell Metabolism》上，被本期编辑推荐为Featured Article。

 

脂肪组织里存在大量的巨噬细胞。异常活跃的CD11c表型的巨噬细胞会产生大量的至炎细胞因子，导致脂肪细胞对胰岛素产生耐受性。

 

研究小组通过遗传技术在一个小时内快速杀死这些“坏的”巨噬细胞，结果可逆转胰岛素耐受现象。令科学家意想不到的是，逆转胰岛素耐受的速度极快，24小时后，动物机体细胞对胰岛素不再耐受，血糖水平变得正常。尽管模型动物仍旧肥胖，胰岛素却开始发挥正常的功效。

 

实验通过转基因技术将白喉毒素受体转染到动物体内，以研究CD11c缺失的小鼠发生的变化。结果表明，缺失CD11c表型巨噬细胞的小鼠很快恢复对胰岛素的敏感性。更令科学家们意想不到的是，缺失CD11c巨噬细胞还能显著地减轻小鼠的炎症反应，不仅能减轻局部的炎症反应还能减轻全身的炎症反应。

 

现在研究成果只在小鼠动物模型上验证过，科学家们说在人类情况不一定完全一致，有待更进一步的深入研究。

 

该研究成果为2型糖尿病的治疗带来新的希望。

 

原文摘要：Ablation of CD11c-Positive Cells Normalizes Insulin Sensitivity in Obese Insulin Resistant Animals

 

【Summary】

Obese adipose tissue is characterized by infiltration of macrophages. We and others recently showed that a specific subset of macrophages is recruited to obese adipose and muscle tissue. This subset expresses CD11c and produces high levels of proinflammatory cytokines that are linked to the development of obesity-associated insulin resistance. Here, we used a conditional cell ablation system, based on transgenic expression of the diphtheria toxin receptor under the control of the CD11c promoter, to study the effects of depletion of CD11c+ cells in obese mouse models. Our results show that CD11c+ cell depletion results in rapid normalization of insulin sensitivity. Furthermore, CD11c+ cell ablation leads to a marked decrease in inflammatory markers, both locally and systemically, as reflected by gene expression and protein levels. Together, these results indicate that these CD11c+ cells are a potential therapeutic target for treatment of obesity-related insulin resistance and type II diabetes.

 

（生物通 张欢）