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Research article - Peer-reviewed, 2010

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

Authors' information

Johansson, Jan
Swedish University of Agricultural Sciences, Department of Anatomy, Physiology and Biochemistry (AFB)

Sustainable Development Goals

SDG3 Good health and wellbeing

UKÄ Subject classification

Biochemistry and Molecular Biology

Publication Identifiers

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

URI (permanent link to this page)

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