Journal article

Pancreatic beta-Cell Membrane Fluidity and Toxicity Induced by Human Islet Amyloid Polypeptide Species

Emily H Pilkington, Esteban N Gurzov, Aleksandr Kakinen, Sara A Litwak, William J Stanley, Thomas P Davis, Pu Chun Ke

Scientific Reports | NATURE PUBLISHING GROUP | Published : 2016

Abstract

Aggregation of human islet amyloid polypeptide (hIAPP) into fibrils and plaques is associated with pancreatic β-cell loss in type 2 diabetes (T2D). However, due to the rapidness of hIAPP conversion in aqueous phase, exactly which hIAPP species is responsible for the observed toxicity and through what mechanisms remains ambiguous. In light of the importance of understanding hIAPP toxicity for T2D here we show a biophysical scheme based on the use of a lipophilic Laurdan dye for examining MIN6 cell membranes upon exposure to fresh and oligomeric hIAPP as well as mature amyloid. It has been found that all three hIAPP species, especially fresh hIAPP, enhanced membrane fluidity and caused losses ..

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Grants

Awarded by ARC


Funding Acknowledgements

This work was supported by ARC Project No. CE140100036 (Davis). Davis is thankful for the award of an Australian Laureate Fellowship from the ARC. Gurzov is supported by a Juvenile Diabetes Research Foundation (JDRF) fellowship. The St Vincent's Institute receives support from the Operational Infrastructure Support Scheme of the Government of Victoria. The authors thank the technical assistances from Drs. Shane Seabrook and Eric Hanssen for the high-throughput DLS and TEM experiments.