Nikolaus Marx, Daniel Walcher, Claudia Raichle, Milos Aleksic, Helga Bach, Miriam Grüb, Vinzenz Hombach, Peter Libby, Arthur Zieske, Satoki Homma, Jack Strong
Department of Internal Medicine II-Cardiology, University of Ulm, Robert-Koch-Str. 8, D-89081 Ulm, Germany. nikolaus.marx@medizin.uni-ulm.de
Arteriosclerosis, thrombosis, and vascular biology 2004 MarIncreased 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. We demonstrate significantly higher intimal C-peptide deposition in thoracic aorta 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. 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.
Nikolaus Marx, Daniel Walcher, Claudia Raichle, Milos Aleksic, Helga Bach, Miriam Grüb, Vinzenz Hombach, Peter Libby, Arthur Zieske, Satoki Homma, Jack Strong. C-peptide colocalizes with macrophages in early arteriosclerotic lesions of diabetic subjects and induces monocyte chemotaxis in vitro. Arteriosclerosis, thrombosis, and vascular biology. 2004 Mar;24(3):540-5
PMID: 14707040
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