title: C-peptide and its C-terminal fragments improve erythrocyte deformability in type 1 diabetes patients.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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 Ca(2+)-dependent and involves activation of red blood cell Na(+), K(+)-ATPase.
authors.affiliation: Department of Internal Medicine, University of Mainz, 55101 Mainz, Germany. thomas hach@mckinsey.com
authors.forename: Thomas
authors.initials: T
authors.lastname: Hach
authors.forename: Thomas
authors.initials: T
authors.lastname: Forst
authors.forename: Thomas
authors.initials: T
authors.lastname: Kunt
authors.forename: Karin
authors.initials: K
authors.lastname: Ekberg
authors.forename: Andreas
authors.initials: A
authors.lastname: Pfützner
authors.forename: John
authors.initials: J
authors.lastname: Wahren
mesh_terms: D000328:Adult; D002096:C-Peptide / Q000097:blood* / Q000737:chemistry; D002118:Calcium / Q000378:metabolism; D016022:Case-Control Studies; D002614:Chelating Agents / Q000494:pharmacology; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D004492:Edetic Acid / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004907:Erythrocyte Deformability / Q000187:drug effects; D004912:Erythrocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D005260:Female; D018056:Hemorheology; D006801:Humans; D008297:Male; D010042:Ouabain / Q000494:pharmacology; D010446:Peptide Fragments / Q000097:blood*; D037342:Pertussis Toxin / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism; D013314:Stress, Mechanical
chemical_list: D002096:C-Peptide; D002614:Chelating Agents; D004791:Enzyme Inhibitors; D010446:Peptide Fragments; D010042:Ouabain; D004492:Edetic Acid; D037342:Pertussis Toxin; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium