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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doaj-8452747042f54cf090beddaab0c7fd412020-12-08T09:14:16ZengNature Publishing GroupScientific Reports2045-23222019-08-019111310.1038/s41598-019-48262-6Protective effect of nobiletin on isolated human islets survival and function against hypoxia and oxidative stress-induced apoptosisSomayeh Keshtkar0Maryam Kaviani1Zahra Jabbarpour2Bita Geramizadeh3Elahe Motevaseli4Saman Nikeghbalian5Alireza Shamsaeefar6Nasrin Motazedian7Ismail H. Al-Abdullah8Mohammad Hossein Ghahremani9Negar Azarpira10Department of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical SciencesTransplant Research Center, Shiraz University of Medical SciencesDepartment of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical SciencesTransplant Research Center, Shiraz University of Medical SciencesDepartment of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical SciencesShiraz Organ Transplant Center, Shiraz University of Medical SciencesShiraz Organ Transplant Center, Shiraz University of Medical SciencesTransplant Research Center, Shiraz University of Medical SciencesDepartment of Translational Research and Cellular Therapeutics, Diabetes and Metabolism Research Institute, Beckman Research Institute of City of HopeDepartment of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical SciencesTransplant Research Center, Shiraz University of Medical SciencesAbstract 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.https://doi.org/10.1038/s41598-019-48262-6 |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
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 |
spellingShingle |
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 Scientific Reports |
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 Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2019-08-01 |
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. |
url |
https://doi.org/10.1038/s41598-019-48262-6 |
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