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Research article2010Peer reviewed

Oligomerization and insulin interactions of proinsulin C-peptide: Threefold relationships to properties of insulin

Jornvall, Hans; Lindahl, Emma; Astorga-Wells, Juan; Lind, Jesper; Holmlund, Anna; Melles, Ermias; Alvelius, Gunvor; Nerelius, Charlotte; Maler, Lena; Johansson, Jan

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-mu M). 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. (c) 2009 Elsevier Inc. All rights reserved.

Keywords

Proinsulin C-peptide; Insulin degrading enzyme; Oligomerization; Mass spectrometry; Diabetes types 1 and 2; Peptide deposits

Published in

Biochemical and Biophysical Research Communications
2010, Volume: 391, number: 3, pages: 1561-1566 Publisher: ACADEMIC PRESS INC ELSEVIER SCIENCE

    Sustainable Development Goals

    SDG3 Good health and well-being

    UKÄ Subject classification

    Biochemistry and Molecular Biology

    Publication identifier

    DOI: https://doi.org/10.1016/j.bbrc.2009.12.125

    Permanent link to this page (URI)

    https://res.slu.se/id/publ/48651