Human synthetic islet amyloid polypeptide (hIAPP) is rapidly converted to β-sheet conformation and fibrils in aqueous media. Optimal solubility conditions for hIAPP were determined by circular dichroism spectroscopy and transmission electron microscopy. hIAPP in trifluoroethanol or hexafluoro-2-isopropanol (HFIP) diluted in water or phosphate buffer (PB) exhibited random structure which was converted to β-sheet and fibrils with time. hIAPP, solubilised in HFIP, filtered and lyophilised remained in stable random structure for up to 7 days in water; in PB, insoluble aggregates precipitated from which protofilaments and fibrils formed with time. This suggests that amorphous aggregates of hIAPP could initiate islet amyloidosis in vivo.
