Effects of beta cell granule components on human islet amyloid polypeptide fibril formation

FEBS Letters

Steiner, Donald F.²  Westermark, Gunilla T.¹  Leckström, Arnold¹  Westermark, Per¹  Li, Zhan-Chun¹ 

[1] Department of Pathology, Linköping University, Linköping, Sweden;Department of Biochemistry and Molecular Biology and the Howard Hughes Medical Institute, University of Chicago, Chicago, IL, USA

关键词: Fibril;    Islet amyloid polypeptide;    Non-insulin-dependent diabetes mellitus;    In vitro;    Granule;   

DOI  :  10.1016/0014-5793(95)01512-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown