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doi:10.1016/0014-5793(95)01512-4 
Copyright © 1996 Published by Elsevier Science B.V.
Research letter
Effects of beta cell granule components on human islet amyloid polypeptide fibril formation
Per Westermarka, 
, Zhan-Chun Lia, Gunilla T. Westermarka, Arnold Leckströma and Donald F. Steinerb
a Department of Pathology, Linköping University, Linköping, Sweden
b Department of Biochemistry and Molecular Biology and the Howard Hughes Medical Institute, University of Chicago, Chicago, IL, USA
Received 1 December 1995.
Abstract
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, Ca2+ and Zn2+ each individually enhanced fibril formation. C-peptide combined with Ca2+ 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, Ca2+ 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.
Author Keywords: Fibril; Islet amyloid polypeptide; Non-insulin-dependent diabetes mellitus; In vitro; Granule
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