title: Oligomerization and insulin interactions of proinsulin C-peptide: Threefold relationships to properties of insulin.
abstract: Three principally different sites of action have been reported for proinsulin C-peptide, at surface-mediated, intracellular, and extracellular locations. Following up on the latter, we now find that (i) mass spectrometric analyses reveal the presence of the C-peptide monomer in apparent equilibrium with a low-yield set of oligomers in weakly acidic or basic aqueous solutions, even at low peptide concentrations (sub-muM). It further shows not only C-peptide to interact with insulin oligomers (known before), but also the other way around. (ii) Polyacrylamide gel electrophoresis of C-peptide shows detectable oligomers upon Western blotting. Formation of thioflavin T positive material was also detected. (iii) Cleavage patterns of analogues are compatible with C-peptide as a substrate of insulin degrading enzyme. Combined, the results demonstrate three links with insulin properties, in a manner reminiscent of amyloidogenic peptides and their chaperons in other systems. If so, peripheral C-peptide/insulin interactions, absolute amounts of both peptides and their ratios may be relevant to consider in diabetic and associated diseases.
authors.affiliation: Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-171 77 Stockholm, Sweden. Hans.Jornvall@ki.se
authors.forename: Hans
authors.initials: H
authors.lastname: Jörnvall
authors.forename: Emma
authors.initials: E
authors.lastname: Lindahl
authors.forename: Juan
authors.initials: J
authors.lastname: Astorga-Wells
authors.forename: Jesper
authors.initials: J
authors.lastname: Lind
authors.forename: Anna
authors.initials: A
authors.lastname: Holmlund
authors.forename: Ermias
authors.initials: E
authors.lastname: Melles
authors.forename: Gunvor
authors.initials: G
authors.lastname: Alvelius
authors.forename: Charlotte
authors.initials: C
authors.lastname: Nerelius
authors.forename: Lena
authors.initials: L
authors.lastname: Mäler
authors.forename: Jan
authors.initials: J
authors.lastname: Johansson
mesh_terms: D052160:Benzothiazoles; D002096:C-Peptide / Q000737:chemistry*; D005456:Fluorescent Dyes / Q000737:chemistry; D006801:Humans; D007328:Insulin / Q000737:chemistry*; D055550:Protein Stability; D021241:Spectrometry, Mass, Electrospray Ionization; D013844:Thiazoles / Q000737:chemistry
chemical_list: D052160:Benzothiazoles; D002096:C-Peptide; D005456:Fluorescent Dyes; D007328:Insulin; D013844:Thiazoles; C009462:thioflavin T