C-Peptide Induces Chemotaxis of Human CD4-Positive Cells

Abstract

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.