Skip to main content

Research Repository

Advanced Search

Further insight into the role of metals in amyloid formation by IAPP1-37 and ProIAPP1-48

Further insight into the role of metals in amyloid formation by IAPP1-37 and ProIAPP1-48 Thumbnail


Background: IAPP1-37 and ProIAPP1-48 are amyloidogenic peptides implicated in ß-cell death in diabetes. Interactions with metals may be involved in both the cytotoxicity of these peptides and their deposition as amyloids associated with diabetes-related pathologies.

Methods: We have used the complementary methods of thioflavin T (ThT) fluorescence and transmission
electron microscopy (TEM) to investigate the role of seeds and specifically metal-peptide seeds in accelerating amyloid formation by ProIAPP. In addition we have used these complementary methods alongside dynamic light scattering (DLS) to observe the dynamics of IAPP amyloid formation during the earliest phase of peptide aggregation.

Results: Seeding universally resulted in an acceleration of amyloid formation, as indicated by increased ThT fluorescence, over the shorter term (minutes) while having no influence upon total amyloid deposits (no differences in ThT fluorescence) over many days. Only copper-peptide seeds were ineffective in accelerating amyloid formation above that observed for sham seeds (no peptide). Different seeding environments resulted in amyloid deposits of different fibrillar and non-fibrillar morphologies following longer term incubations regardless of the uniform nature of the respective measurements of ThT fluorescence. The aggregation dynamics of IAPP, mimicking its secretion into extracellular milieus, were complex and suggested that while metals at equimolar, generally increased rates of aggregation, with the possible exception of Cu(II), the range of sub-micron and micron-sized particles observed were not easily explained by either measurement of ThT fluorescence or imaging by TEM.

Conclusions: Seeding may be significant in accelerating the formation of amyloid and in influencing the final morphologies of deposited amyloids but not in determining the total deposits of amyloid. It was of interest that copper-peptide seeds did not accelerate amyloid formation in the shorter term and this could indicate an incompatible seeding morphology due to copper? This first attempt to monitor aggregation dynamics of IAPP over only minutes has shown direct impact of metals on peptide particle size which could have implications for the cytotoxicity of IAPP in diabetes.


(2015). Further insight into the role of metals in amyloid formation by IAPP1-37 and ProIAPP1-48.

Acceptance Date Dec 11, 2015
Publication Date Dec 23, 2015
Journal Journal of Diabetes Research and Clinical Metabolism
Print ISSN 2050-0866
Keywords Diabetes, metals, amyloid, amylin, IAPP, ProIAPP, ThT fluorescence, TEM, DLS
Publisher URL


Downloadable Citations