Evidence for the link between defective autophagy and inflammation in peripheral blood mononuclear cells of type 2 diabetic patients

Abstract

Autophagy was shown to modulate inflammation in immune cells. This study was designed to evaluate the association between autophagy and inflammation in peripheral blood mononuclear cells (PBMCs) of type 2 diabetic (T2D) and non-diabetic (ND) subjects. The autophagy markers were measured by real-time PCR and western blot. The gene expression of pro- and anti-inflammatory cytokines was assessed by real-time PCR. Reduced transcription of BECN1 and LAMP2 and unchanged expression of MAP1LC3B and ATG5 were observed in PBMCs of T2D patients. Decreased LC3B-II and increased p62/SQSTM1 levels were found in PBMCs of diabetic patients. The p-mTOR level was higher in PBMCs of diabetic patients. An increase in both IL-1β and TNF-α gene expression, along with a decrease in the expression of IL-10, was observed in PBMCs of T2D patients. TNF-α mRNA expression was inversely correlated with the mRNA expression of BECN1 and LAMP2. TNF-α and IL-1β expression were negatively correlated with the protein levels of LC3B-II. TNF-α and IL-1β expression had also a positive correlation with protein level of p62. IL-10 mRNA expression was positively correlated with the mRNA expression of BECN1 and LAMP2 and protein levels of LC3B-II and negatively correlated with protein level of p62. In addition, p-mTOR level was positively correlated with IL-1β and TNF-α mRNA expression. The results revealed a reduced autophagy in PBMCs of T2D patients that is liked with an enhanced inflammation. The suppression of autophagy in PBMCs of diabetic patients may be associated with the activation of the mTOR signaling.

The synergistic effect of fenretinide and metformin to achieve a decrease in insulin resistance and inflammatory mediators: an in vivo study

“…On the other hand, IL-10 exhibits beneficial metabolic effects (Donia et al 2016;Ip et al 2017). Our findings are similar to those of Alizadeh et al (2018) who revealed a lower mRNA expression of IL-10 in type 2 diabetic patients compared to non-diabetic subjects. Thus, reduced levels of serum IL-10 might lead to type 2 diabetes.…”

Alteration of autophagy-related protein 5 (ATG5) levels and Atg5 gene expression in diabetes mellitus with and without complications

“…Our results coincide with several clinical studies that have been published, showing that Atg5, Atg8, and LC3 mRNA level were found to be largely reduced in the renal tissue of DN patients. 29,30…”

Immunomodulatory Properties of Adipose-Derived Stem Cells Treated with 5-Azacytydine and Resveratrol on Peripheral Blood Mononuclear Cells and Macrophages in Metabolic Syndrome Animals

“…Interestingly, LAMP-2 down-regulation in PBMCs cultured with ASC EMS may be a novel mechanism that connects obesity and inflammation in EMS horses. It was shown that reduced autophagy in PBMCs in type 2 diabetes patients was correlated with an enhanced inflammation [ 36 ]. Therefore, it is tempting to speculate that rejuvenated ASCs with AZA/RES will affect the physiological properties of PBMCs after clinical application in EMS individuals by triggering autophagy, and, in consequence, diminishing the inflammatory state of the animal body.…”