c-peptide and Aortic-Diseases

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.. 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.

Topics: Adolescent; Adult; Androstadienes; Aorta, Thoracic; Aortic Diseases; Arteriosclerosis; C-Peptide; Cells, Cultured; Chemotaxis; Chromones; Diabetes Mellitus, Type 2; Disease Progression; Enzyme Inhibitors; Female; GTP-Binding Proteins; Humans; Hyperinsulinism; Insulin Resistance; Macrophages; Male; Metabolic Syndrome; Models, Biological; Monocytes; Morpholines; Pertussis Toxin; Phosphatidylinositol 3-Kinases; Wortmannin