NR4A1 is associated with chronic low-grade inflammation in patients with type 2 diabetes.

Qi Huang,Zhe Dai,Li Cai,Fan Yang,Yancheng Xu,Junli Xue,Runmei Zou,Jing Chen,Li Sun

doi:10.3892/etm.2014.1958

Abstract

Type 2 diabetes (T2D) is a common disorder characterized by chronic low-grade inflammation. In the present study, the expression levels of nuclear receptor subfamily 4 group A member 1 (NR4A1) and the correlation with inflammatory cytokine production and free fatty acids (FFAs) in patients with T2D and healthy participants were investigated. NR4A1 expression levels in peripheral blood mononuclear cells (PBMCs) from patients with T2D (n=30) and healthy controls (n=34) were analyzed. In addition, the levels of fasting blood glucose (FBG), fasting plasma insulin (FIN), FFAs, total cholesterol (TC), triglyceride (TG), high-density lipoprotein-cholesterol (HDL-C) and low-density lipoprotein-cholesterol (LDL-C) were analyzed, and the homeostasis model assessment (HOMA) was used to estimate the insulin resistance (IR). Additionally, PBMCs from healthy subjects were cultured with or without 250 μM palmitic acid (PA). Levels of NR4A1, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the PBMCs were also analyzed. The basal expression levels of NR4A1, TNF-α and IL-6 were higher in the T2D patients when compared with the controls. In addition, the levels of FFAs, TG and LDL-C, as well as the HOMA-IR, were higher in T2D patients. Furthermore, NR4A1 expression was demonstrated to positively correlate with the HOMA-IR and the levels of FFAs, TNF-α, IL-6, FIN and FBG. Furthermore, 250 μM PA stimulation was shown to increase NR4A1 expression and the secretion of inflammatory cytokines in the cultured PBMCs. Therefore, increased NR4A1 expression levels are correlated with a chronic low-grade inflammatory state and the disorder of lipid metabolism in patients with T2D.

Highlights

The incidence of diabetes is increasing, with the disease affecting ~347 million adults worldwide [1], which is projected to increase to 552 million by 2030 [2]
Statistically significant differences were identified in the BMI, fasting blood glucose (FBG), fasting plasma insulin (FIN), TG, total cholesterol (TC), low‐density lipoprotein‐cholesterol (LDL‐C) and high‐density lipoprotein‐cholesterol (HDL‐C) in patients with Type 2 diabetes (T2D) compared with the control group
A statistically significant increase was observed in the homeostasis model assessment (HOMA)‐insulin resistance (IR) for T2D patients (5.06±2.41 vs. 1.35±0.25, P

Summary

Introduction

The incidence of diabetes is increasing, with the disease affecting ~347 million adults worldwide [1], which is projected to increase to 552 million by 2030 [2]. Increasing evidence indicates that inflammation is involved in the pathogenesis of T2D, with levels of C‐reactive protein (CRP), a biomarker of inflammation, increased in patients that are obese and diabetic [3,4,5]. Prospective studies have demonstrated that higher plasma levels of CRP, fibrinogen, IL‐6 and PAI may be used to predict the risk of developing T2D [3,6,7,8,9]. Investigations by Nakanishi et al [10] indicated that a higher white blood cell count may predict the development of impaired fasting glucose and T2D. Results from clinical trials have shown that the administration of anti‐inflammatory agents, such as IL‐1 antagonists, in patients with T2D significantly lowered blood glucose levels, as well as CRP, IL‐6 and other inflammatory biomarkers [12,13]

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