C-Peptide and Its C-Terminal Fragments Improve Erythrocyte Deformability in Type 1 Diabetes Patients. (6th May 2008)

• Record Type: Journal Article
• Authors: Hach, Thomas; Forst, Thomas; Kunt, Thomas; Ekberg, Karin; Pfützner, Andreas; Wahren, John
• Other Names: Chakrabarti Subrata Academic Editor.
• Is Part Of: Experimental diabetes research. Volume 2008(2008)
• Publication Date: 2008-05-06
• Subjects: Diabetes -- Research -- Periodicals; Diabetes -- Research; Periodicals; 616.462
• DOI: 10.1155/2008/730594
• Languages: English
• ISSNs: 1687-5214

Abstract

Abstract : Aims/hypothesis . Data now indicate that proinsulin C-peptide exerts important physiological effects and shows the characteristics of an endogenous peptide hormone. This study aimed to investigate the influence of C-peptide and fragments thereof on erythrocyte deformability and to elucidate the relevant signal transduction pathway. Methods . Blood samples from 23 patients with type 1 diabetes and 15 matched healthy controls were incubated with 6.6 nM of either human C-peptide, C-terminal hexapeptide, C-terminal pentapeptide, a middle fragment comprising residues 11–19 of C-peptide, or randomly scrambled C-peptide. Furthermore, red blood cells from 7 patients were incubated with C-peptide, penta- and hexapeptides with/without addition of ouabain, EDTA, or pertussis toxin. Erythrocyte deformability was measured using a laser diffractoscope in the shear stress range 0.3–60 Pa. Results . Erythrocyte deformability was impaired by 18–25% in type 1 diabetic patients compared to matched controls in the physiological shear stress range 0.6–12 Pa( P < .01 – .001 ) . C-peptide, penta- and hexapeptide all significantly improved the impaired erythrocyte deformability of type 1 diabetic patients, while the middle fragment and scrambled C-peptide had no detectable effect. Treatment of erythrocytes with ouabain or EDTA completely abolished the C-peptide, penta- and hexapeptide effects. Pertussis toxin in itself significantly increased erythrocyte deformability. Conclusion/interpretation . C-peptide and its C-terminal fragments are equally effective in improving erythrocyte deformability in type 1 diabetes. The C-terminal residues of C-peptide are causally involved in this effect. The signal transduction pathway isCa 2 + -dependent and involves activation of red blood cellNa +, K + -ATPase.