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Dysregulation of Gene Expression of Key Signaling Mediators in PBMCs from People with Type 2 Diabetes Mellitus

Nilofer Qureshi1,2, Julia Desousa1,2, Adeela Z Siddiqui1

  • 1Department of Biomedical Sciences, Shock/Trauma Research Center, School of Medicine, University of Missouri-Kansas City, 2411 Holmes Street, Kansas City, MO 64108, USA.

International Journal of Molecular Sciences
|February 11, 2023
PubMed

Insights

People with type 2 diabetes exhibit impaired inflammatory gene responses to bacterial toxins. This suggests a mechanism for their increased susceptibility to infections and chronic inflammation.

Area of Science:

  • Immunology
  • Metabolic Disorders
  • Molecular Biology

Background:

  • Type 2 Diabetes Mellitus (DM2) is a leading cause of death, associated with increased susceptibility to infections and inflammation.
  • The precise mechanisms underlying DM2 and its link to immune dysfunction are not fully understood.
  • Previous research showed resveratrol (RES) downregulates inflammatory gene expression in peripheral blood mononuclear cells (PBMCs).

Purpose of the Study:

  • To investigate the ex vivo response of PBMCs from people with type 2 diabetes (PwD2) to bacterial lipopolysaccharide (LPS) and soybean lectin (LEC).
  • To compare gene expression patterns in PwD2 with those in non-diabetic controls upon stimulation with LPS and LEC.
  • To assess the effect of resveratrol on inflammatory gene expression in PwD2.

Main Methods:

  • Peripheral blood mononuclear cells (PBMCs) were isolated from people with type 2 diabetes and non-diabetic controls.
  • Cells were stimulated ex vivo with bacterial lipopolysaccharide (LPS) and soybean lectin (LEC).
  • Next-generation sequencing (NGS) was used to analyze the gene expression profiles, including proteasome subunits and inflammatory mediators.

Main Results:

  • PBMCs from PwD2 showed significantly reduced upregulation of key inflammatory genes (e.g., PSMB8, STAT1, HLA, TNF-α) in response to LPS and LEC compared to non-diabetic controls.
  • Genes involved in proteasome function, T cell signaling, and antigen presentation were notably repressed in PwD2.
  • Resveratrol further downregulated inflammatory gene expression in PwD2 PBMCs.

Conclusions:

  • PwD2 exhibit an impaired inflammatory gene response to common bacterial toxins.
  • This dampened response may contribute to the heightened susceptibility of individuals with type 2 diabetes to infections.
  • The findings suggest a link between impaired immune cell function, inflammation, insulin resistance, and metabolic changes in type 2 diabetes.
Keywords:
IFN-γLPSNGSNOcytokineslectinsresveratrolsignal transductiontype 2 diabetes

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