Pancreatic β-Cell Membrane Fluidity and Toxicity Induced by Human Islet Amyloid Polypeptide Species
| Autor: | Thomas P. Davis, William J Stanley, Emily H. Pilkington, Aleksandr Kakinen, Pu Chun Ke, Esteban Nicolas Gurzov, Sara A Litwak |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty Amyloid Cell Survival Membrane Fluidity Cell Amylin Biology Reactive Oxygen Species -- metabolism Article Cell Line Cell membrane 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cell Membrane -- drug effects -- metabolism Insulin-Secreting Cells Membrane fluidity medicine Humans Viability assay Insulin-Secreting Cells -- drug effects -- metabolism chemistry.chemical_classification Reactive oxygen species Multidisciplinary Islet Amyloid Polypeptide -- pharmacology Cell Membrane Sciences bio-médicales et agricoles Cell Survival -- drug effects Islet Amyloid Polypeptide 030104 developmental biology medicine.anatomical_structure chemistry Membrane Fluidity -- drug effects Biophysics Reactive Oxygen Species Laurdan 030217 neurology & neurosurgery |
| Zdroj: | Scientific Reports Scientific reports, 6 |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep21274 |
| Popis: | 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 in cell viability. The cell generation of reactive oxygen species (ROS), however, was the most pronounced with mature amyloid hIAPP. The correlation between changes in membrane fluidity and cell viability and their lack of correlation with ROS production suggest hIAPP toxicity is elicited through both physical and biochemical means. This study offers a new insight into β-cell toxicity induced by controlled hIAPP species, as well as new biophysical methodologies that may prove beneficial for the studies of T2D as well as neurological disorders. info:eu-repo/semantics/published |
| Databáze: | OpenAIRE |
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