PAR level mediates the link between ROS and inflammatory response in patients with type 2 diabetes mellitus

Area of Science:

• Biochemistry
• Immunology
• Endocrinology

Background:

• Type 2 diabetes mellitus (T2DM) involves disrupted glucose homeostasis, oxidative stress, and inflammation.
• Poly(ADP-ribosyl)ation (PARylation) is a post-translational modification implicated in T2DM pathophysiology.
• Clinical evidence linking PARylation, oxidative stress, and inflammation in human T2DM is limited.

Purpose of the Study:

• To investigate the relationship between oxidative stress, PARylation, and inflammatory response in T2DM patients.
• To explore the clinical relevance of PARylation in T2DM pathophysiology.

Main Methods:

• Cross-sectional study of 61 T2DM patients and 48 controls.
• Quantification of PAR levels in peripheral blood mononuclear cells (PBMC) using ELISA.
• Assessment of oxidative stress markers (d-ROMs, antioxidant power) in plasma and PBMC.
• Measurement of antioxidant enzyme (SOD1, GPX1, CAT) and inflammatory mediator (IL6, TNF-α, CD68, MCP1) gene expression in PBMC via qPCR.

Main Results:

• T2DM patients showed elevated PAR levels in PBMC and increased plasma d-ROMs.
• Positive association between PAR levels and d-ROMs, indicating a link between oxidative stress and PAR metabolism.
• Oxidative stress (d-ROMs) mediated the association between HbA1c and PAR levels.
• Elevated PAR levels correlated with increased expression of pro-inflammatory cytokines IL6 and TNF-α in PBMC.

Conclusions:

• Hyperactivated PARylation is associated with poor glycemic control and oxidative stress in T2DM.
• Increased PAR levels correlate with upregulated inflammatory mediators in T2DM.
• Further research is needed to validate findings and explore clinical implications of PARylation in T2DM.