2型糖尿病患者中AIM2和循环线粒体DNA水平升高。
Increased Levels of AIM2 and Circulating Mitochondrial DNA in Type 2 Diabetes.
作者信息
Cataño Cañizales Yolanda Guadalupe, Uresti Rivera Edith Elena, García Jacobo Rocío Edith, Portales Perez Diana Patricia, Yadira Bastian, Rodriguez Rivera Jaime Guillermo, Amaro Roberto Gonzalez, Enciso Moreno José Antonio, García Hernández Mariana Haydee
机构信息
Medical Research Unit-Zacatecas, Mexican Institute for Social Security-IMSS, Zacatecas, Mexico.
出版信息
Iran J Immunol. 2018 Jun;15(2):142-155.
BACKGROUND
Chronic inflammation has critical role in Type 2 diabetes (T2D), in which IL-1β contributes in insulin resistance and beta cell dysfunction. The activation of NLRP3 and AIM2 by endogens ligands, such as mtDNA can lead to the release of active form of IL-1β.
OBJECTIVE
To evaluate AIM2 expression and activation as well as circulating mtDNA levels in T2D patients.
METHODS
AIM2 expression was analyzed by flow cytometry, it's activity was assessed by measuring in vitro release of IL-1β induced by Poly (dA:dT), and mtDNA copy number was determined by quantitative real-time polymerase chain reaction.
RESULTS
Increased percent of AIM2+ cells were detected in monocytes from patients with T2D. Moreover, increased levels of IL-1β in monocytes cultures from T2D patients compared to healthy controls were observed. Also, association between AIM2+ cells and hyperglycemia (r=0.4385, P=0.0095) and triglycerides levels (r=0.5112, P=0.002) and waist-hip ratio (r=0.4710, P=0.0049) were detected. Likewise, the mtDNA copy number was augmented in T2D patients compared to control group. The mtDNA copies number was associated with body mass index (r=0.4231, P=0.0008) and TNF-α levels (r=0.5231, P=0.0005). In addition, increased levels of IL-12p70, TNF-a, IL-10, IL-6, IL-8 and IL-1β were detected in a serum from T2D patients.
CONCLUSION
These results suggest the involvement of AIM2 and mtDNA in the inflammatory process seen in T2D.
背景
慢性炎症在2型糖尿病（T2D）中起关键作用，其中白细胞介素-1β（IL-1β）导致胰岛素抵抗和β细胞功能障碍。内源性配体（如线粒体DNA）激活NLRP3和AIM2可导致活性形式的IL-1β释放。
目的
评估2型糖尿病患者中AIM2的表达、激活情况以及循环线粒体DNA水平。
方法
通过流式细胞术分析AIM2表达，通过测量聚（dA:dT）诱导的IL-1β体外释放评估其活性，通过定量实时聚合酶链反应测定线粒体DNA拷贝数。
结果
在2型糖尿病患者的单核细胞中检测到AIM2+细胞百分比增加。此外，与健康对照相比，观察到2型糖尿病患者单核细胞培养物中IL-1β水平升高。还检测到AIM2+细胞与高血糖（r=0.4385，P=0.0095）、甘油三酯水平（r=0.5112，P=0.002）和腰臀比（r=0.4710，P=0.0049）之间存在关联。同样，与对照组相比，2型糖尿病患者的线粒体DNA拷贝数增加。线粒体DNA拷贝数与体重指数（r=0.4231，P=0.0008）和肿瘤坏死因子-α（TNF-α）水平（r=0.5231，P=0.0005）相关。此外，在2型糖尿病患者的血清中检测到IL-12p70、TNF-α、IL-10、IL-6、IL-8和IL-1β水平升高。
结论
这些结果表明AIM2和线粒体DNA参与了2型糖尿病中的炎症过程。
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