Sammanfattning

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.

Nyckelord

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

Publicerad i

Biochemical and Biophysical Research Communications
2010, Volym: 391, nummer: 3, sidor: 1561-1566
Utgivare: ACADEMIC PRESS INC ELSEVIER SCIENCE

SLU författare

• Johansson, Jan

  • Institutionen för husdjurens biovetenskaper, Sveriges lantbruksuniversitet
    

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UKÄ forskningsämne

Biokemi och molekylärbiologi


Publikationens identifierare

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

Permanent länk till denna sida (URI)

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