Oligomerization and insulin interactions of proinsulin C-peptide: Threefold relationships to properties of insulin.
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.
Jörnvall
Hans
H
Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-171 77 Stockholm, Sweden. Hans.Jornvall@ki.se
Lindahl
Emma
E
Astorga-Wells
Juan
J
Lind
Jesper
J
Holmlund
Anna
A
Melles
Ermias
E
Alvelius
Gunvor
G
Nerelius
Charlotte
C
Mäler
Lena
L
Johansson
Jan
J
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
D052160:Benzothiazoles; D002096:C-Peptide; D005456:Fluorescent Dyes; D007328:Insulin; D013844:Thiazoles; C009462:thioflavin T