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Rodriguez Camargo, D.C. ; Tripsianes, K.* ; Buday, K. ; Frankó, A. ; Göbl, C. ; Hartlmüller, C.* ; Sarkar, R. ; Aichler, M. ; Mettenleiter, G. ; Schulz, M. ; Böddrich, A.* ; Erck, C.* ; Martens, H.* ; Walch, A.K. ; Madl, T. ; Wanker, E.E.* ; Conrad, M. ; Hrabě de Angelis, M. ; Reif, B.

The redox environment triggers conformational changes and aggregation of hIAPP in Type II Diabetes.

Sci. Rep. 7:44041 (2017)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Type II diabetes (T2D) is characterized by diminished insulin production and resistance of cells to insulin. Among others, endoplasmic reticulum (ER) stress is a principal factor contributing to T2D and induces a shift towards a more reducing cellular environment. At the same time, peripheral insulin resistance triggers the over-production of regulatory hormones such as insulin and human islet amyloid polypeptide (hIAPP). We show that the differential aggregation of reduced and oxidized hIAPP assists to maintain the redox equilibrium by restoring redox equivalents. Aggregation thus induces redox balancing which can assist initially to counteract ER stress. Failure of the protein degradation machinery might finally result in β-cell disruption and cell death. We further present a structural characterization of hIAPP in solution, demonstrating that the N-terminus of the oxidized peptide has a high propensity to form an α-helical structure which is lacking in the reduced state of hIAPP. In healthy cells, this residual structure prevents the conversion into amyloidogenic aggregates.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
ISSN (print) / ISBN 2045-2322
e-ISSN 2045-2322
Quellenangaben Volume: 7, Issue: , Pages: , Article Number: 44041 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Non-patent literature Publications
Reviewing status Peer reviewed