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

Thomas Hach,Karin Ekberg,Thomas Kunt,John Wahren,Andreas Pfützner,Thomas Forst

doi:10.1155/2008/730594

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 is Ca2+-dependent and involves activation of red blood cell Na+, K+-ATPase.

Highlights

During the past decade, several studies have provided evidence that C-peptide is a biologically active endogenous peptide
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)
Erythrocyte deformability was significantly decreased in type 1 diabetes patients compared to healthy controls over the full range of shear stress tested (Figure 1)

Summary

Introduction

Several studies have provided evidence that C-peptide is a biologically active endogenous peptide. Studies in patients with type 1 diabetes who lack endogenous C-peptide production show that administration of Cpeptide in replacement doses results in increased regional blood flow in several tissues [11,12,13] and amelioration of diabetes-induced functional and structural abnormalities of the peripheral nerves and the kidneys [14,15,16]. It is well established that diabetes is associated with reduced deformability of red blood cells [19,20,21]. This abnormality is of clinical significance in that it compromises the ability of red blood cells to pass through capillaries, reduces tissue perfusion, and impairs tissue oxygen supply [4, 22].

Objectives

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Results

Conclusion