C-peptide induces chemotaxis of human CD4-positive cells: Involvement of pertussis toxin-sensitive G-proteins and phosphoinositide 3-kinase

Daniel Walcher, Milos Aleksic, Verena Jerg, Vinzenz Hombach, Arthur Zieske, Satoki Homma, Jack Strong, Nikolaus Marx

Research output: Contribution to journalArticle

58 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1664-1670
Number of pages7
JournalDiabetes
Volume53
Issue number7
DOIs
StatePublished - Jul 2004

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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