Abstract
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.
Highlights
Inhibitors of dipeptidyl peptidase-IV (DPP-IV), which decrease the degradation of glucose-lowering Glucagon-like peptide-1 (GLP-1)(736) to the metabolically inactive GLP-1(9-36), are current new treatment options for patients with type 2 diabetes mellitus, a high-risk population for cardiovascular disease
Further studies are needed to assess whether such effects may be clinically relevant for patients with type 2 diabetes treated with DPP-IV inhibitors
Similar results were seen when RANTES was used as an inductor of CD4positive lymphocyte migration (Fig. 1B) suggesting that the action of GLP-1(9-36) on T-cell migration is independent of the chemokine used
Summary
Inhibitors of dipeptidyl peptidase-IV (DPP-IV), which decrease the degradation of glucose-lowering GLP-1(736) to the metabolically inactive GLP-1(9-36), are current new treatment options for patients with type 2 diabetes mellitus, a high-risk population for cardiovascular disease. We have previously demonstrated that GLP-1(137), a long and untruncated form of GLP-1, inhibits chemokineinduced CD4-positive lymphocytes migration, an early and critical step of atherogenesis [8,9]. This effect was shown to be dependent on the GLP-1 receptor protein and exendin-4, a specific GLP-1 receptor agonist, had similar effects on T-cell migration. The effects of the metabolite GLP-1(9-36) on human CD4-positive lymphocyte migration are unknown
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
