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

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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.

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Abbreviations

AMPK:

AMP-activated protein kinase

DBP:

Diastolic blood pressure

IL-6:

Interleukin 6

IL-1β:

Interleukin 1β

LC3B:

Light chain 3B

LAMP-2:

Lysosome-associated membrane protein 2

MAP1LC3B:

Microtubule-associated protein 1 light chain 3 beta

mTOR:

Mammalian target of rapamycin

PBMC:

Peripheral blood mononuclear cell

SBP:

Systolic blood pressure

TNF-α:

Tumor necrosis factor alpha

T2D:

Type 2 diabetes

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Acknowledgements

We greatly appreciate the assistance provided by the staff of the Endocrinology and Metabolism Research Institute of Tehran University of Medical Sciences. We also thank all volunteers for their participation in the study. This work was financially supported by grants from the Deputy of Research, Tehran University of Medical Sciences (grant 91-03-30-19266).

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Authors and Affiliations

  1. Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Islamic Republic of Iran

    Samira Alizadeh, Hossein Mazloom, Solaleh Emamgholipour, Abolfazl Golestani & Reza Meshkani

  2. Department of Biochemistry, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Islamic Republic of Iran

    Asie Sadeghi

  3. Department of Immunology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Islamic Republic of Iran

    Farshid Noorbakhsh

  4. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Islamic Republic of Iran

    Mohsen Khoshniatnikoo

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  1. Samira Alizadeh
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Contributions

SA: Conducted research, analyzed data or performed statistical analysis, wrote paper. HM: Conducted research. AS: Conducted research. SE: Wrote paper. AG: Edited paper. FN: Analyzed data or performed statistical analysis. MKN: Helped in patients’ recruitment. RM: Designed research, analyzed data, or performed statistical analysis, had primary responsibility for final content.

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Correspondence to Reza Meshkani.

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Alizadeh, S., Mazloom, H., Sadeghi, A. et al. Evidence for the link between defective autophagy and inflammation in peripheral blood mononuclear cells of type 2 diabetic patients. J Physiol Biochem 74, 369–379 (2018). https://doi.org/10.1007/s13105-018-0624-2

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