Increased T cell immunoglobulin and mucin domain containing 4 (TIM-4) is negatively correlated with serum concentrations of interleukin-1β in type 2 diabetes

J Diabetes. 2016 Mar;8(2):199-205. doi: 10.1111/1753-0407.12276. Epub 2015 Apr 9.

Abstract

Background: T cell immunoglobulin and mucin domain containing 4 (TIM-4), a novel immune regulator, is selectively expressed on antigen-presenting cells, especially macrophages and mature dendritic cells. Although TIM-4 plays key roles in mutiple immune diseases, whether it is involved in type 2 diabetes mellitus (T2D) remains unknown. The aim of the present study was to investigate the expression of TIM-4 in T2D and determine its significance in disease progression.

Methods: Peripheral blood mononuclear cells (PBMC) were isolated from T2D patients and healthy controls to measure TIM-4 mRNA expression by real-time polymerase chain reaction (PCR), and sera were collected to determine interleukin (IL)-1β concentrations and other clinical indicators (high-sensitivity C-reactive protein [hsCRP], total cholesterol, low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol, triglyceride, fasting glucose, HbA1c, aspartate aminotransferase, and alanine aminotransferase).

Results: Expression of TIM-4 mRNA was increased significantly in PBMCs from T2D patients compared with healthy controls. There was a positive correlation between TIM-4 mRNA expression and serum concentrations of hsCRP. However, there was a negative correlation between TIM-4 mRNA expression and IL-1β concentrations, indicating the potential role for TIM-4 to negatively regulate IL-1β production. In addition, TIM-4 mRNA expression was negatively correlated with lowLDL-C, and there was a tendency for a negative relationship between TIM-4 mRNA expression and HbA1c.

Conclusions: The results of the present study indicate that TIM-4 contributes, at least in part, to the pathogenesis of T2D, possibly by regulating IL-1β.

Keywords: 2型糖尿病; IL-1β; T cell immunoglobulin and mucin domain containing 4 (TIM-4); TIM-4; interleukin-1β; type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alanine Transaminase / blood
  • Aspartate Aminotransferases / blood
  • Blood Glucose / metabolism
  • C-Reactive Protein / metabolism
  • Cells, Cultured
  • Cholesterol / blood
  • Cholesterol, HDL / blood
  • Cholesterol, LDL / blood
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / genetics
  • Fasting / blood
  • Female
  • Glycated Hemoglobin / metabolism
  • Humans
  • Interleukin-1beta / blood*
  • Leukocytes, Mononuclear / metabolism*
  • Male
  • Membrane Proteins / blood*
  • Membrane Proteins / genetics
  • Middle Aged
  • Reverse Transcriptase Polymerase Chain Reaction
  • Triglycerides / classification

Substances

  • Blood Glucose
  • Cholesterol, HDL
  • Cholesterol, LDL
  • Glycated Hemoglobin A
  • Interleukin-1beta
  • Membrane Proteins
  • TIMD4 protein, human
  • Triglycerides
  • C-Reactive Protein
  • Cholesterol
  • Aspartate Aminotransferases
  • Alanine Transaminase