Published online before print January 5, 2004, doi: 10.1161/01.ATV.0000116027.81513.68
© 2004 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
C-Peptide Colocalizes with Macrophages in Early Arteriosclerotic Lesions of Diabetic Subjects and Induces Monocyte Chemotaxis In Vitro
From the Department of Internal Medicine II–Cardiology (N.M., D.W., C.R., M.A., H.B., M.G., V.H.), University of Ulm, Germany; the Department of Medicine (P.L.), Leducq Center for Cardiovascular Research, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA; and the Health Sciences Center (A.Z., S.H., J.S.), Louisiana State University, New Orleans, LA.
Correspondence to Nikolaus Marx, MD, Department of Internal Medicine II–Cardiology, University of Ulm, Robert-Koch-Str. 8, D-89081 Ulm, Germany. E-Mail nikolaus.marx{at}medizin.uni-ulm.de
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.
Key Words: C-peptide • monocytes • diabetes • arteriosclerosis
This article has been cited by other articles:
 |
|
 |
|
  S. R. de Rooij, G. Nijpels, P. M. Nilsson, J. J. Nolan, R. Gabriel, E. Bobbioni-Harsch, G. Mingrone, J. M. Dekker, and for the Relationship Between Insulin Sensitivity a Low-Grade Chronic Inflammation in the Relationship between Insulin Sensitivity and Cardiovascular Disease (RISC) Population: Associations with insulin resistance and cardiometabolic risk profile Diabetes Care, July 1, 2009; 32(7): 1295 - 1301. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Imhof, R. Blagieva, N. Marx, and W. Koenig Drinking modulates monocyte migration in healthy subjects: a randomised intervention study of water, ethanol, red wine and beer with or without alcohol Diabetes and Vascular Disease Research, March 1, 2008; 5(1): 48 - 53. [Abstract] [PDF]
|
|
|
|
 |
|
 L. Langouche, S. Vander Perre, P. J. Wouters, A. D'Hoore, T. K. Hansen, and G. Van den Berghe Effect of Intensive Insulin Therapy on Insulin Sensitivity in the Critically Ill J. Clin. Endocrinol. Metab., October 1, 2007; 92(10): 3890 - 3897. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. D. Chang, G. K. Sukhova, P. Libby, E. Schvartz, A. H. Lichtenstein, S. J. Field, C. Kennedy, S. Madhavarapu, J. Luo, D. Wu, et al. Deletion of the phosphoinositide 3-kinase p110{gamma} gene attenuates murine atherosclerosis PNAS, May 8, 2007; 104(19): 8077 - 8082. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Bruemmer C-Peptide in Insulin Resistance and Vascular Complications: Teaching an Old Dog New Tricks Circ. Res., November 24, 2006; 99(11): 1149 - 1151. [Full Text] [PDF]
|
|
|
|
|
|
D. Walcher, C. Babiak, P. Poletek, S. Rosenkranz, H. Bach, S. Betz, R. Durst, M. Grub, V. Hombach, J. Strong, et al. C-Peptide Induces Vascular Smooth Muscle Cell Proliferation: Involvement of Src-Kinase, Phosphatidylinositol 3-Kinase, and Extracellular Signal-Regulated Kinase 1/2 Circ. Res., November 24, 2006; 99(11): 1181 - 1187. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. T. Bloomgarden Third Annual World Congress on the Insulin Resistance Syndrome: Atherothrombotic disease Diabetes Care, August 1, 2006; 29(8): 1973 - 1980. [Full Text] [PDF]
|
|
|
|
 |
|
 K. Isoda, J. L. Young, A. Zirlik, L. A. MacFarlane, N. Tsuboi, N. Gerdes, U. Schonbeck, and P. Libby Metformin Inhibits Proinflammatory Responses and Nuclear Factor-{kappa}B in Human Vascular Wall Cells Arterioscler Thromb Vasc Biol, March 1, 2006; 26(3): 611 - 617. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. M. Al-Rasheed, R. S. Chana, R. J. Baines, G. B. Willars, and N. J. Brunskill Ligand-independent Activation of Peroxisome Proliferator-activated Receptor-{gamma} by Insulin and C-peptide in Kidney Proximal Tubular Cells: DEPENDENT ON PHOSPHATIDYLINOSITOL 3-KINASE ACTIVITY J. Biol. Chem., November 26, 2004; 279(48): 49747 - 49754. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Walcher and N. Marx Insulin resistance and cardiovascular disease: the role of PPAR{gamma} activators beyond their anti-diabetic action Diabetes and Vascular Disease Research, October 1, 2004; 1(2): 76 - 81. [Abstract] [PDF]
|
|
|
|
 |
|
 D. Walcher, M. Aleksic, V. Jerg, V. Hombach, A. Zieske, S. Homma, J. Strong, and N. Marx C-Peptide Induces Chemotaxis of Human CD4-Positive Cells: Involvement of Pertussis Toxin-Sensitive G-Proteins and Phosphoinositide 3-Kinase Diabetes, July 1, 2004; 53(7): 1664 - 1670. [Abstract] [Full Text] [PDF]
|
|