Protective effect of nobiletin on isolated human islets survival and function against hypoxia and oxidative stress-induced apoptosis

Abstract Islets transplantation, as a treatment of type 1 diabetes, faces challenges, including the loss of islets in the process of isolation and pre-transplantation due to cellular stresses-induced apoptosis. Accordingly, the optimization of culture plays a decisive role in the transplantation suc...

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Autores principales: Somayeh Keshtkar, Maryam Kaviani, Zahra Jabbarpour, Bita Geramizadeh, Elahe Motevaseli, Saman Nikeghbalian, Alireza Shamsaeefar, Nasrin Motazedian, Ismail H. Al-Abdullah, Mohammad Hossein Ghahremani, Negar Azarpira
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Publicado: Nature Portfolio 2019
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spelling oai:doaj.org-article:8452747042f54cf090beddaab0c7fd412021-12-02T16:08:52ZProtective effect of nobiletin on isolated human islets survival and function against hypoxia and oxidative stress-induced apoptosis10.1038/s41598-019-48262-62045-2322https://doaj.org/article/8452747042f54cf090beddaab0c7fd412019-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-48262-6https://doaj.org/toc/2045-2322Abstract Islets transplantation, as a treatment of type 1 diabetes, faces challenges, including the loss of islets in the process of isolation and pre-transplantation due to cellular stresses-induced apoptosis. Accordingly, the optimization of culture plays a decisive role in the transplantation success. In this study, we evaluated the effect of nobiletin on the cultured human islets. Isolated human islets were treated by different concentrations of nobiletin and cultured for 24 and 72 hours. Then, the islets viability, apoptosis, insulin and C-peptide secretion, and apoptosis markers were evaluated. Also, the production of reactive oxygen species (ROS), hypoxia inducible factor 1 alpha (HIF-1α), and its target genes in the islets were examined. Our findings showed that the islets were encountered with hypoxia and oxidative stress after isolation and during culture. These insults induced apoptosis and reduced viability during culture period. Moreover, the secretion of insulin and C-peptide decreased. Nobiletin treatments significantly improved the islets survival through reduction of HIF-1α and ROS production and suppression of apoptosis, along with increased islets function. Islet protective effect of nobiletin might be related to its anti-oxidant, anti-apoptotic and insulinotropic properties. Hence, in order to achieve viable and functional islets for clinical transplantation, the application of nobiletin during pre-transplantation period is useful.Somayeh KeshtkarMaryam KavianiZahra JabbarpourBita GeramizadehElahe MotevaseliSaman NikeghbalianAlireza ShamsaeefarNasrin MotazedianIsmail H. Al-AbdullahMohammad Hossein GhahremaniNegar AzarpiraNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-13 (2019)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Somayeh Keshtkar
Maryam Kaviani
Zahra Jabbarpour
Bita Geramizadeh
Elahe Motevaseli
Saman Nikeghbalian
Alireza Shamsaeefar
Nasrin Motazedian
Ismail H. Al-Abdullah
Mohammad Hossein Ghahremani
Negar Azarpira
Protective effect of nobiletin on isolated human islets survival and function against hypoxia and oxidative stress-induced apoptosis
description Abstract Islets transplantation, as a treatment of type 1 diabetes, faces challenges, including the loss of islets in the process of isolation and pre-transplantation due to cellular stresses-induced apoptosis. Accordingly, the optimization of culture plays a decisive role in the transplantation success. In this study, we evaluated the effect of nobiletin on the cultured human islets. Isolated human islets were treated by different concentrations of nobiletin and cultured for 24 and 72 hours. Then, the islets viability, apoptosis, insulin and C-peptide secretion, and apoptosis markers were evaluated. Also, the production of reactive oxygen species (ROS), hypoxia inducible factor 1 alpha (HIF-1α), and its target genes in the islets were examined. Our findings showed that the islets were encountered with hypoxia and oxidative stress after isolation and during culture. These insults induced apoptosis and reduced viability during culture period. Moreover, the secretion of insulin and C-peptide decreased. Nobiletin treatments significantly improved the islets survival through reduction of HIF-1α and ROS production and suppression of apoptosis, along with increased islets function. Islet protective effect of nobiletin might be related to its anti-oxidant, anti-apoptotic and insulinotropic properties. Hence, in order to achieve viable and functional islets for clinical transplantation, the application of nobiletin during pre-transplantation period is useful.
format article
author Somayeh Keshtkar
Maryam Kaviani
Zahra Jabbarpour
Bita Geramizadeh
Elahe Motevaseli
Saman Nikeghbalian
Alireza Shamsaeefar
Nasrin Motazedian
Ismail H. Al-Abdullah
Mohammad Hossein Ghahremani
Negar Azarpira
author_facet Somayeh Keshtkar
Maryam Kaviani
Zahra Jabbarpour
Bita Geramizadeh
Elahe Motevaseli
Saman Nikeghbalian
Alireza Shamsaeefar
Nasrin Motazedian
Ismail H. Al-Abdullah
Mohammad Hossein Ghahremani
Negar Azarpira
author_sort Somayeh Keshtkar
title Protective effect of nobiletin on isolated human islets survival and function against hypoxia and oxidative stress-induced apoptosis
title_short Protective effect of nobiletin on isolated human islets survival and function against hypoxia and oxidative stress-induced apoptosis
title_full Protective effect of nobiletin on isolated human islets survival and function against hypoxia and oxidative stress-induced apoptosis
title_fullStr Protective effect of nobiletin on isolated human islets survival and function against hypoxia and oxidative stress-induced apoptosis
title_full_unstemmed Protective effect of nobiletin on isolated human islets survival and function against hypoxia and oxidative stress-induced apoptosis
title_sort protective effect of nobiletin on isolated human islets survival and function against hypoxia and oxidative stress-induced apoptosis
publisher Nature Portfolio
publishDate 2019
url https://doaj.org/article/8452747042f54cf090beddaab0c7fd41
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