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Effects of beta cell granule components on human islet amyloid polypeptide fibril formation
Author(s) -
Westermark Per,
Li Zhan-Chun,
Westermark Gunilla T.,
Leckström Arnold,
Steiner Donald F.
Publication year - 1996
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(95)01512-4
Subject(s) - islet , fibrillogenesis , fibril , proinsulin , chemistry , granule (geology) , peptide , amyloid (mycology) , biochemistry , in vitro , amylin , biophysics , insulin , microbiology and biotechnology , endocrinology , biology , inorganic chemistry , paleontology
Formation of amyloid‐like fibrils in a solution of human islet amyloid polypeptide (hIAPP) with and without the presence of other β‐cell granule components was studied in vitro. Insulin at less than equimolar concentration strongly inhibited hIAPP fibrillogenesis. Proinsulin had a weaker inhibitory effect while C‐peptide, Ca 2+ and Zn 2+ each individually enhanced fibril formation. C‐peptide combined with Ca 2+ had an inhibitory effect. Since IAPP was found almost exclusively in the halo fractions of isolated islet secretory granules, primarily the concentrations of C‐peptide, Ca 2+ and possibly proinsulin may be crucial for the native state of IAPP. It is concluded that an imbalance between fibril formation enhancers and inhibitors may be of importance in the pathogenesis of amyloid in the islets of Langerhans.