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Experimental Diabetes Research
Volume 2008 (2008), Article ID 730594, 6 pages
http://dx.doi.org/10.1155/2008/730594
Research Article

C-Peptide and Its C-Terminal Fragments Improve Erythrocyte Deformability in Type 1 Diabetes Patients

1Department of Internal Medicine, University of Mainz, 55101 Mainz, Germany
2McKinsey & Company, Inc., Am Sandtorkai 77, 20457 Hamburg, Germany
3Institute for Clinical Research and Development, 55116 Mainz, Germany
4Department of Internal Medicine, Zayed Military Hospital, P.O. Box 3740, Abu Dhabi, United Arab Emirates
5Department of Molecular Medicine and Surgery, Section of Clinical Physiology, Karolinska Institute, 17177 Stockholm, Sweden

Received 9 October 2007; Accepted 27 February 2008

Academic Editor: Subrata Chakrabarti

Copyright © 2008 Thomas Hach et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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 . 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 is -dependent and involves activation of red blood cell ,-ATPase.