C-peptide exerts antithrombotic effects that are repressed by insulin in normal and diabetic mice

• Published in: Diabetologia Vol. 49; no. 4; pp. 792 - 800
• Main Authors: Lindenblatt, N, Braun, B, Menger, M. D, Klar, E, Vollmar, B
• Format: Journal Article
• Language: English
• Published: Berlin Berlin/Heidelberg : Springer-Verlag 01.04.2006; Springer; Springer Nature B.V
• Subjects: Animals; Biological and medical sciences; Blood clots; c-peptide; C-Peptide - therapeutic use; Diabetes; Diabetes Mellitus - drug therapy; Diabetes Mellitus - metabolism; Diabetes. Impaired glucose tolerance; Disease Models, Animal; Dose-Response Relationship, Drug; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Endothelium; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Flow Cytometry; Humans; Immunohistochemistry; In vivo microscopy; Insulin; Insulin - pharmacology; Laboratory animals; Medical sciences; Mice; Microcirculation - drug effects; Microscopy; Microvascular thrombosis; Nitric oxide; P-Selectin - metabolism; Patients; Peptides; Plasminogen Activator Inhibitor 1 - metabolism; Platelet Glycoprotein GPIIb-IIIa Complex - metabolism; Platelets; streptozotocin; Surgery; Thrombosis; Thrombosis - complications; Thrombosis - drug therapy; Thrombosis - metabolism; Germany; Endocrinopathy; Pancreatic hormone; Microvascular thrombosis; Diabetes mellitus; Rodentia; Cardiovascular disease; Insulin; C-Peptide; Thrombosis; Vascular disease; In vivo microscopy; In vivo; Microcirculation; Vertebrata; Platelet; Mammalia; Mouse; Animal; Diabetes; Platelets; Streptozotocin
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/s00125-006-0152-4

Aims/hypothesis Diabetic macro- and microangiopathy are associated with a high risk of vascular complications. The diabetic patient exhibits a pathological coagulation state, with an increased synthesis of coagulation factors and plasminogen activator inhibitor 1 (PAI-1) as well as an enhanced aggregation of platelets. Previous studies have shown that C-peptide can reduce leucocyte-endothelial cell interaction and improve microvascular blood flow in patients with type 1 diabetes. In the present study, we examined in vivo whether C-peptide is able to reduce platelet activation and through that microvascular thrombus formation. Materials and methods In the microvessels of cremaster muscle preparations taken from normal and diabetic mice, ferric chloride-induced thrombus formation was analysed using intravital fluorescence microscopy. Results I.V. administration of C-peptide in high dose (70 nmol/kg), but not in low dose (7 nmol/kg), caused a significant delay in arteriolar and venular thrombus growth in normal and diabetic mice. This effect was repressed by cremaster muscle superfusion with insulin (100 μU/ml) in diabetic animals, but particularly in normal animals. In parallel, immunohistochemistry demonstrated a higher number of PAI-1-expressing vessels in cremaster muscle tissue from control animals and from animals treated with C-peptide and insulin compared with tissue from animals with C-peptide treatment application alone. Conclusions/interpretation We conclude that C-peptide possesses antithrombotic actions in vivo. A causal role of PAI-1 in this scenario needs to be further addressed. However, the reversal of C-peptide action by insulin may invalidate the use of this peptide as a treatment option to improve rheology and microcirculation in diabetic patients.