C-peptide induces chemotaxis of human CD4-positive cells: involvement of pertussis toxin-sensitive G-proteins and phosphoinositide 3-kinase.
Increased levels of C-peptide, a cleavage product of proinsulin, circulate in patients with insulin resistance and early type 2 diabetes, a high-risk population for the development of a diffuse and extensive pattern of arteriosclerosis. The present study examined the effect of C-peptide on CD4(+) lymphocyte migration, an important process in early atherogenesis. C-peptide stimulated CD4(+) cell chemotaxis in a concentration-dependent manner. This process involves pertussis toxin-sensitive G-proteins as well as activation of phosphoinositide 3-kinase (PI 3-K). Biochemical analysis showed that C-peptide induced recruitment of PI 3-K to the cell membrane as well as PI 3-K activation in human CD4(+) cells. In addition, antidiabetic peroxisome proliferator-activated receptor gamma-activating thiazolidinediones inhibited C-peptide-induced CD4(+) cell chemotaxis as well as PI 3-Kgamma activation. Finally, immunofluorescence staining of thoracic artery specimen of diabetic patients showed intimal CD4(+) cells in areas with C-peptide deposition. Thus, C-peptide might deposit in the arterial intima in diabetic patients during early atherogenesis and subsequently attract CD4(+) cells to migrate into the vessel wall.
Walcher
Daniel
D
Department of Internal Medicine II-Cardiology, University of Ulm, Germany.
Aleksic
Milos
M
Jerg
Verena
V
Hombach
Vinzenz
V
Zieske
Arthur
A
Homma
Satoki
S
Strong
Jack
J
Marx
Nikolaus
N
D001161:Arteriosclerosis / Q000378:metabolism / Q000473:pathology; D002096:C-Peptide / Q000378:metabolism / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000502:physiology*; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D002633:Chemotaxis / Q000502:physiology*; D003925:Diabetic Angiopathies / Q000378:metabolism / Q000473:pathology; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D037342:Pertussis Toxin / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D045162:Thiazolidinediones / Q000494:pharmacology
D002096:C-Peptide; D045162:Thiazolidinediones; D037342:Pertussis Toxin; D019869:Phosphatidylinositol 3-Kinases; D019204:GTP-Binding Proteins