The redox environment triggers conformational changes and aggregation of hIAPP in Type II Diabetes.
Sci Rep
; 7: 44041, 2017 03 13.
Article
in En
| MEDLINE
| ID: mdl-28287098
ABSTRACT
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 ß-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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Diabetes Mellitus, Type 2
/
Islet Amyloid Polypeptide
Limits:
Animals
/
Female
/
Humans
Language:
En
Journal:
Sci Rep
Year:
2017
Document type:
Article
Affiliation country: