Glucagon-like peptide-1(1-37) inhibits chemokine-induced migration of human CD4-positive lymphocytes

Cell Mol Life Sci. 2010 Oct;67(20):3549-55. doi: 10.1007/s00018-010-0396-5. Epub 2010 May 21.


The present study examined the effect of GLP-1(1-37) on chemokine-induced CD4-positive lymphocyte migration as an early and critical step in atherogenesis. Pretreatment with GLP-1(1-37) reduced the SDF-induced migration of isolated human CD4-positive lymphocytes in a concentration-dependent manner. Similar effects were seen when RANTES was used as a chemokine. GLP-1(1-37)'s effect on CD4-positive lymphocyte migration was mediated through an early inhibition of chemokine-induced PI-3 kinase activity. Downstream, GLP-1(1-37) inhibited SDF-induced phosphorylation of MLC and cofilin and limited f-actin formation as well as ICAM3 translocation. Furthermore, exendin-4 inhibited SDF-induced migration of CD4-positive lymphocytes similarly to GLP-1(1-37), and transfection of these cells with GLP-1 receptor siRNA abolished GLP-1(1-37)'s action on chemokine-induced ICAM3 translocation, suggesting an effect mediated via the GLP-1 receptor. Thus, GLP-1(1-37) inhibits chemokine-induced CD4-positive lymphocyte migration by inhibition of the PI3-kinase pathway and via the GLP-1 receptor. This effect provides a potential novel mechanism for how GLP-1(1-37) may modulate vascular disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Depolymerizing Factors / metabolism
  • Actins / metabolism
  • Antigens, CD / metabolism
  • CD4-Positive T-Lymphocytes / cytology*
  • CD4-Positive T-Lymphocytes / drug effects*
  • CD4-Positive T-Lymphocytes / enzymology
  • Cell Adhesion Molecules / metabolism
  • Cell Movement / drug effects*
  • Chemokine CXCL12 / pharmacology*
  • Enzyme Activation / drug effects
  • Glucagon-Like Peptide 1 / pharmacology*
  • Glucagon-Like Peptide-1 Receptor
  • Humans
  • Myosin Light Chains / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphorylation / drug effects
  • Protein Transport / drug effects
  • RNA, Small Interfering / metabolism
  • Receptors, Glucagon / metabolism
  • Transfection


  • Actin Depolymerizing Factors
  • Actins
  • Antigens, CD
  • Cell Adhesion Molecules
  • Chemokine CXCL12
  • GLP1R protein, human
  • Glucagon-Like Peptide-1 Receptor
  • ICAM3 protein, human
  • Myosin Light Chains
  • RNA, Small Interfering
  • Receptors, Glucagon
  • Glucagon-Like Peptide 1
  • Phosphatidylinositol 3-Kinases