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

Abstract EN

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.