B-CELL GRANULE PEPTIDES AFFECT HUMAN ISLET AMYLOID POLYPEPTIDE (IAPP)FIBRIL FORMATION IN-VITRO

Islet amyloid polypeptide (IAPP) forms fibrils spontaneously. We exami ned whether other B cell granule peptides affect formation of beta-ple ated sheet fibrils in vitro from human IAPP. Quantitative radioassay ( radioactivity of soluble IAPP after adding I-125-IAPP) and thioflavine fluorescence spectroscopy showed that insulin, C-peptide, and pancrea statin inhibited fibril formation by 60-100% at ratio 100:1 (peptide:I APP), whereas at 1:10 or 1:100, i.e., IAPP in excess, a potentiated IA PP fibril formation was induced by the peptides. Semi-quantitative ana lysis by electron microscopy yielded similar effects. Thus, spontaneou s IAPP fibrillisation is influenced by other B cell secretory granule peptides in a molar ratio dependent manner. (C) 1997 Academic Press.