Influence of insulin therapy on expression of chemokine receptor CCR5 and selected inflammatory markers in patients with type 2 diabetes mellitus

Int J Clin Pharmacol Ther. 2007 Oct;45(10):563-7. doi: 10.5414/cpp45563.

Abstract

Objective: Leukocyte migration to the subendothelial space is considered crucial in the initiation of atherosclerosis. There is increasing evidence that overexpression of chemokine receptors contribute to this process. CCR5 is one of the receptors present on peripheral T lymphocytes, monocytes and macrophages. We decided to evaluate the expression of CCR5 on monocytes and macrophages in peripheral blood and selected inflammatory markers in patients with type 2 diabetes mellitus before and after the initiation of insulin therapy.

Material and methods: A total of 10 patients with newly diagnosed type 2 diabetes and 6 healthy control subjects were studied. Assessment of CCR5 expression on the surface of monocytes and macrophages in peripheral blood was performed using flow cytometry before the initiation of insulin therapy and after 5-week treatment. Serum concentrations of RANTES, TNF-alpha, IL-6 and hsCRP were assessed.

Results: When compared to control subjects, we observed higher densities of CCR5 on the surface of peripheral blood monocytes and macrophages and higher concentrations of RANTES, TNF-alpha, IL-6 and hsCRP before insulin therapy. After 5-week insulin therapy, there was a significant decrease in the expression of CCR5 on the surface of these cells and a significant fall in serum levels of RANTES, IL-6, TNF-alpha and hsCRP.

Conclusions: Type 2 diabetes leads to an increase in the inflammatory process, and insulin therapy inhibits the early stages of this process.

Publication types

  • Controlled Clinical Trial

MeSH terms

  • Aged
  • C-Reactive Protein / metabolism
  • Chemokine CCL5 / metabolism
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism
  • Female
  • Flow Cytometry
  • Gene Expression Regulation
  • Humans
  • Hypoglycemic Agents / pharmacology*
  • Inflammation Mediators / metabolism*
  • Insulin / pharmacology*
  • Interleukin-6 / metabolism
  • Macrophages / metabolism
  • Male
  • Middle Aged
  • Monocytes / metabolism
  • Receptors, CCR5 / drug effects*
  • Receptors, CCR5 / genetics
  • Receptors, CCR5 / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Chemokine CCL5
  • Hypoglycemic Agents
  • Inflammation Mediators
  • Insulin
  • Interleukin-6
  • Receptors, CCR5
  • Tumor Necrosis Factor-alpha
  • C-Reactive Protein