Decreased expression levels of Nurr1 are associated with chronic inflammation in patients with type 2 diabetes

Mol Med Rep. 2015 Oct;12(4):5487-93. doi: 10.3892/mmr.2015.4105. Epub 2015 Jul 21.

Abstract

Chronic inflammation is associated with insulin resistance, a characteristic of type 2 diabetes (T2D). Nuclear receptor‑related protein 1 (Nurr1) can regulate inflammation, dependent on the nature of individual diseases. However, whether Nurr1 regulates chronic inflammation during the pathogenic process of T2D in humans remains to be fully elucidated. The present study aimed to investigate the potential association between the expression of Nurr1 in peripheral blood mononuclear cells (PBMCs) and inflammation in patients with T2D. The levels of plasma tumor necrosis factor (TNF)α and interleukin (IL)‑6, the relative expression levels of Nurr1, and glycogen synthase kinase (GSK)‑3β phosphorylation in PBMCs from 40 patients with T2D and 40 healthy controls (HC group) were examined, and their potential association with clinical measures were analyzed. The expression levels of Nurr1, induced by high glucose and palmitic acid, were assessed in the PBMCs from the HC group. Compared with the HC group, significantly higher levels of plasma TNFα and IL‑6 were correlated positively with the degree of insulin resistance in the T2D patients. However, significantly lower expression levels of Nurr1 and GSK‑3β phosphorylation in the PBMCs were correlated negatively with the levels of TNFα, IL‑6, fasting insulin and insulin resistance in the T2D patients. Treatment of the PBMCs with high glucose or palmitic acid inhibited the expression of Nurr1 in a dose‑ and time‑dependent manner. Therefore, decreased expression levels of Nurr1 were associated with chronic inflammation and insulin resistance in patients with T2D.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers
  • Blood Glucose
  • Case-Control Studies
  • Chronic Disease
  • Cytokines / blood
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / genetics*
  • Down-Regulation
  • Female
  • Gene Expression Regulation*
  • Glycogen Synthase Kinase 3
  • Glycogen Synthase Kinase 3 beta
  • Humans
  • Inflammation / blood
  • Inflammation / etiology*
  • Inflammation Mediators / blood
  • Insulin Resistance
  • Leukocytes, Mononuclear / metabolism
  • Male
  • Middle Aged
  • Nuclear Receptor Subfamily 4, Group A, Member 2 / genetics*
  • Palmitic Acid / metabolism
  • Phosphorylation

Substances

  • Biomarkers
  • Blood Glucose
  • Cytokines
  • Inflammation Mediators
  • Nuclear Receptor Subfamily 4, Group A, Member 2
  • Palmitic Acid
  • GSK3B protein, human
  • Glycogen Synthase Kinase 3 beta
  • Glycogen Synthase Kinase 3