Aggregation of the diabetes-related peptide ProIAPP1-48 measured by dynamic light scattering

Abstract

Islet amyloid polypeptide (IAPP_1-37) or amylin is implicated in the aetiology of diabetes. It is found as amyloid along with its precursor ProIAPP_1-48 in the islets of Langerhans in the pancreas. Metals have been implicated in amyloidogenesis of both IAPP and ProIAPP. Herein we have used dynamic light scattering (DLS) to investigate how Al(III) and Cu(II) influence aggregation of ProIAPP_1-48 under near-physiological conditions and in a biologically-relevant timeframe. ProIAPP_1-48 formed primarily sub-micron particles within 5 min (e.g. 470 nm at 15μM peptide) that grew to micron-sized particles (1310 nm) within a 30 min timeframe. Equimolar Al(III) had little influence upon particle size at either 5 (656 nm) or 30 min (1250 nm) while Cu(II) tended to increase particle size over the same time period (731-1300 nm). It is suggested that any effects of Al(III) and Cu(II) reflected their well known tendencies to support β-sheet or amorphous aggregates of ProIAPP_1-48 respectively.

Keywords: Aluminium in biology; Amylin; Amyloid: aggregation; Copper in biology; Dynamic light scattering; IAPP; ProIAPP.