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Benzbromarone, Quercetin, and Folic Acid Inhibit Amylin Aggregation

Human Amylin, or islet amyloid polypeptide (hIAPP), is a small hormone secreted by pancreatic β-cells that forms aggregates under insulin deficiency metabolic conditions, and it constitutes a pathological hallmark of type II diabetes mellitus. In type II diabetes patients, amylin is abnormally incre...

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Autores principales: López, Laura C., Varea, Olga, Navarro, Susanna, Carrodeguas, José A., Sanchez de Groot, Natalia, Ventura, Salvador, Sancho, Javier
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4926496/
https://www.ncbi.nlm.nih.gov/pubmed/27322259
http://dx.doi.org/10.3390/ijms17060964
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author López, Laura C.
Varea, Olga
Navarro, Susanna
Carrodeguas, José A.
Sanchez de Groot, Natalia
Ventura, Salvador
Sancho, Javier
author_facet López, Laura C.
Varea, Olga
Navarro, Susanna
Carrodeguas, José A.
Sanchez de Groot, Natalia
Ventura, Salvador
Sancho, Javier
author_sort López, Laura C.
collection PubMed
description Human Amylin, or islet amyloid polypeptide (hIAPP), is a small hormone secreted by pancreatic β-cells that forms aggregates under insulin deficiency metabolic conditions, and it constitutes a pathological hallmark of type II diabetes mellitus. In type II diabetes patients, amylin is abnormally increased, self-assembled into amyloid aggregates, and ultimately contributes to the apoptotic death of β-cells by mechanisms that are not completely understood. We have screened a library of approved drugs in order to identify inhibitors of amylin aggregation that could be used as tools to investigate the role of amylin aggregation in type II diabetes or as therapeutics in order to reduce β-cell damage. Interestingly, three of the compounds analyzed—benzbromarone, quercetin, and folic acid—are able to slow down amylin fiber formation according to Thioflavin T binding, turbidimetry, and Transmission Electron Microscopy assays. In addition to the in vitro assays, we have tested the effect of these compounds in an amyloid toxicity cell culture model and we have found that one of them, quercetin, has the ability to partly protect cultured pancreatic insulinoma cells from the cytotoxic effect of amylin. Our data suggests that quercetin can contribute to reduce oxidative damage in pancreatic insulinoma β cells by modulating the aggregation propensity of amylin.
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spelling pubmed-49264962016-07-06 Benzbromarone, Quercetin, and Folic Acid Inhibit Amylin Aggregation López, Laura C. Varea, Olga Navarro, Susanna Carrodeguas, José A. Sanchez de Groot, Natalia Ventura, Salvador Sancho, Javier Int J Mol Sci Article Human Amylin, or islet amyloid polypeptide (hIAPP), is a small hormone secreted by pancreatic β-cells that forms aggregates under insulin deficiency metabolic conditions, and it constitutes a pathological hallmark of type II diabetes mellitus. In type II diabetes patients, amylin is abnormally increased, self-assembled into amyloid aggregates, and ultimately contributes to the apoptotic death of β-cells by mechanisms that are not completely understood. We have screened a library of approved drugs in order to identify inhibitors of amylin aggregation that could be used as tools to investigate the role of amylin aggregation in type II diabetes or as therapeutics in order to reduce β-cell damage. Interestingly, three of the compounds analyzed—benzbromarone, quercetin, and folic acid—are able to slow down amylin fiber formation according to Thioflavin T binding, turbidimetry, and Transmission Electron Microscopy assays. In addition to the in vitro assays, we have tested the effect of these compounds in an amyloid toxicity cell culture model and we have found that one of them, quercetin, has the ability to partly protect cultured pancreatic insulinoma cells from the cytotoxic effect of amylin. Our data suggests that quercetin can contribute to reduce oxidative damage in pancreatic insulinoma β cells by modulating the aggregation propensity of amylin. MDPI 2016-06-18 /pmc/articles/PMC4926496/ /pubmed/27322259 http://dx.doi.org/10.3390/ijms17060964 Text en © 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
López, Laura C.
Varea, Olga
Navarro, Susanna
Carrodeguas, José A.
Sanchez de Groot, Natalia
Ventura, Salvador
Sancho, Javier
Benzbromarone, Quercetin, and Folic Acid Inhibit Amylin Aggregation
title Benzbromarone, Quercetin, and Folic Acid Inhibit Amylin Aggregation
title_full Benzbromarone, Quercetin, and Folic Acid Inhibit Amylin Aggregation
title_fullStr Benzbromarone, Quercetin, and Folic Acid Inhibit Amylin Aggregation
title_full_unstemmed Benzbromarone, Quercetin, and Folic Acid Inhibit Amylin Aggregation
title_short Benzbromarone, Quercetin, and Folic Acid Inhibit Amylin Aggregation
title_sort benzbromarone, quercetin, and folic acid inhibit amylin aggregation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4926496/
https://www.ncbi.nlm.nih.gov/pubmed/27322259
http://dx.doi.org/10.3390/ijms17060964
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