Increased levels of AIM2 and circulating mitochondrial DNA in type 2 diabetes
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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%2b 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%2b 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. © 2018, Shiraz University of Medical Sciences. All rights reserved.
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AIM2; Cell-free mtDNA; IL-1β; Inflammasome; Type 2 Diabetes absent in melanoma 2; cryopyrin; hemoglobin A1c; high density lipoprotein cholesterol; inflammasome; interleukin 10; interleukin 12p70; interleukin 1beta; interleukin 6; mitochondrial DNA; tumor necrosis factor; unclassified drug; AIM2 protein, human; autacoid; biological marker; cell free nucleic acid; DNA binding protein; inflammasome; interleukin 1beta; mitochondrial DNA; adult; Article; body mass; controlled study; creatinine blood level; cytokine production; density gradient centrifugation; DNA isolation; enzyme activation; enzyme linked immunosorbent assay; female; flow cytometry; gene dosage; glucose blood level; human; hyperglycemia; immunostimulation; inflammation; low density lipoprotein cholesterol level; major clinical study; male; middle aged; non insulin dependent diabetes mellitus; peripheral blood mononuclear cell; protein expression; real time polymerase chain reaction; triacylglycerol blood level; waist hip ratio; Western blotting; blood; case control study; gene expression; genetics; metabolism; monocyte; non insulin dependent diabetes mellitus; Adult; Biomarkers; Case-Control Studies; Cell-Free Nucleic Acids; Diabetes Mellitus, Type 2; DNA, Mitochondrial; DNA-Binding Proteins; Female; Flow Cytometry; Gene Expression; Humans; Inflammasomes; Inflammation Mediators; Interleukin-1beta; Male; Middle Aged; Monocytes
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