C-Peptide Colocalizes with Macrophages in Early Arteriosclerotic Lesions of Diabetic Subjects and Induces Monocyte Chemotaxis In Vitro

Nikolaus Marx, Daniel Walcher, Claudia Raichle, Milos Aleksic, Helga Bach, Miriam Grüb, Vinzenz Hombach, Peter Libby, Arthur Zieske, Satoki Homma, Jack Strong

Research output: Contribution to journalArticle

81 Scopus citations

Abstract

Objective-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. This study tested the hypothesis that C-peptide might participate in atherogenesis in these patients. Method and Results-We demonstrate significantly higher intimal C-peptide deposition in thoracic artery specimens from young diabetic subjects compared with matched nondiabetic controls as determined by immunohistochemical staining. C-peptide colocalized with monocytes/macrophages in the arterial intima of artery specimen from diabetic subjects. In vitro, C-peptide stimulated monocyte chemotaxis in a concentration-dependent manner with a maximal 2.3±0.4-fold increase at 1 nmol/L C-peptide. Pertussis toxin, wortmannin, and LY294002 inhibited C-peptide-induced monocyte chemotaxis, suggesting the involvement of pertussis toxin-sensitive G-proteins as well as a phosphoinositide 3-kinase (PI3K)-dependent mechanism. In addition, C-peptide treatment activated PI3K in human monocytes, as demonstrated by PI3K activity assays. Conclusion-C-peptide accumulated in the vessel wall in early atherogenesis in diabetic subjects and may promote monocyte migration into developing lesions. These data support the hypothesis that C-peptide may play an active role in atherogenesis in diabetic patients and suggest a new mechanism for accelerated arterial disease in diabetes.

Original languageEnglish (US)
Pages (from-to)540-545
Number of pages6
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume24
Issue number3
DOIs
StatePublished - Mar 2004

Keywords

  • Arteriosclerosis
  • C-peptide
  • Diabetes
  • Monocytes

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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