Increased Levels of AIM2 and Circulating Mitochondrial DNA in Type 2 Diabetes

Iran J Immunol. 2018 Jun;15(2):142-155.

Abstract

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.

MeSH terms

  • Adult
  • Biomarkers
  • Case-Control Studies
  • Cell-Free Nucleic Acids*
  • DNA, Mitochondrial* / blood
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / diagnosis
  • Diabetes Mellitus, Type 2 / genetics*
  • Female
  • Flow Cytometry
  • Gene Expression*
  • Humans
  • Inflammasomes / metabolism
  • Inflammation Mediators / blood
  • Interleukin-1beta / metabolism
  • Male
  • Middle Aged
  • Monocytes / metabolism

Substances

  • AIM2 protein, human
  • Biomarkers
  • Cell-Free Nucleic Acids
  • DNA, Mitochondrial
  • DNA-Binding Proteins
  • Inflammasomes
  • Inflammation Mediators
  • Interleukin-1beta