RT Journal Article
SR Electronic
T1 C-Peptide Induces Chemotaxis of Human CD4-Positive Cells
JF Diabetes
JO Diabetes
FD American Diabetes Association
SP 1664
OP 1670
DO 10.2337/diabetes.53.7.1664
VO 53
IS 7
A1 Walcher, Daniel
A1 Aleksic, Milos
A1 Jerg, Verena
A1 Hombach, Vinzenz
A1 Zieske, Arthur
A1 Homma, Satoki
A1 Strong, Jack
A1 Marx, Nikolaus
YR 2004
UL http://diabetes.diabetesjournals.org/content/53/7/1664.abstract
AB 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 γ–activating thiazolidinediones inhibited C-peptide–induced CD4+ cell chemotaxis as well as PI 3-Kγ 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.