Inhibition of insulin amyloid fibril formation by cyclodextrins.
Amyloid
; 22(3): 181-6, 2015.
Article
in En
| MEDLINE
| ID: mdl-26204452
ABSTRACT
Localized insulin-derived amyloid masses occasionally form at the site of repeated insulin injections in patients with insulin-dependent diabetes and cause subcutaneous insulin resistance. Various kinds of insulin including porcine insulin, human insulin, and insulin analogues reportedly formed amyloid fibrils in vitro and in vivo, but the impact of the amino acid replacement in insulin molecules on amyloidogenicity is largely unknown. In the present study, we demonstrated the difference in amyloid fibril formation kinetics of human insulin and insulin analogues, which suggests an important role of the C-terminal domain of the insulin B chain in nuclear formation of amyloid fibrils. Furthermore, we determined that cyclodextrins, which are widely used as drug carriers in the pharmaceutical field, had an inhibitory effect on the nuclear formation of insulin amyloid fibrils. These findings have significant implications for the mechanism underlying insulin amyloid fibril formation and for developing optimal additives to prevent this subcutaneous adverse effect.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cyclodextrins
/
Insulin Aspart
/
Insulin Detemir
/
Amyloid
/
Insulin
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Amyloid
Journal subject:
BIOQUIMICA
Year:
2015
Document type:
Article
Affiliation country:
Japón