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The efficacy of SPA0355 in protecting β cells in isolated pancreatic islets and in a murine experimental model of type 1 diabetes
Cytokines activate several inflammatory signals that mediate β-cell destruction. We recently determined that SPA0355 is a strong anti-inflammatory compound, thus reporting its efficacy in protecting β cells from various insults. The effects of SPA0355 on β-cell survival were studied in RINm5F cells...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3849566/ https://www.ncbi.nlm.nih.gov/pubmed/24176948 http://dx.doi.org/10.1038/emm.2013.109 |
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author | Bae, Ui-Jin Song, Mi-Young Jang, Hyun-Young Jin Gim, Hyo Ryu, Jae-Ha Lee, Sang-Myeong Jeon, Raok Park, Byung-Hyun |
author_facet | Bae, Ui-Jin Song, Mi-Young Jang, Hyun-Young Jin Gim, Hyo Ryu, Jae-Ha Lee, Sang-Myeong Jeon, Raok Park, Byung-Hyun |
author_sort | Bae, Ui-Jin |
collection | PubMed |
description | Cytokines activate several inflammatory signals that mediate β-cell destruction. We recently determined that SPA0355 is a strong anti-inflammatory compound, thus reporting its efficacy in protecting β cells from various insults. The effects of SPA0355 on β-cell survival were studied in RINm5F cells and primary islets. The protective effects of this compound on the development of type 1 diabetes were evaluated in non-obese diabetic (NOD) mice. SPA0355 completely prevented cytokine-induced nitric oxide synthase (iNOS) expression and cytotoxicity in RINm5F cells and isolated islets. The molecular mechanism of SPA0355 inhibition of iNOS expression involves the inhibition of nuclear factor κB and Janus kinase signal transducer and activator of transcription pathways. The protective effects of SPA0355 against cytokine toxicity were further demonstrated by normal insulin secretion and absence of apoptosis of cytokine-treated islets. In experiments with NOD mice, the occurrence of diabetes was efficiently reduced when the mice were treated with SPA0355. Therefore, SPA0355 might be a valuable treatment option that delays the destruction of pancreatic β cells in type 1 diabetes. |
format | Online Article Text |
id | pubmed-3849566 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-38495662013-12-06 The efficacy of SPA0355 in protecting β cells in isolated pancreatic islets and in a murine experimental model of type 1 diabetes Bae, Ui-Jin Song, Mi-Young Jang, Hyun-Young Jin Gim, Hyo Ryu, Jae-Ha Lee, Sang-Myeong Jeon, Raok Park, Byung-Hyun Exp Mol Med Original Article Cytokines activate several inflammatory signals that mediate β-cell destruction. We recently determined that SPA0355 is a strong anti-inflammatory compound, thus reporting its efficacy in protecting β cells from various insults. The effects of SPA0355 on β-cell survival were studied in RINm5F cells and primary islets. The protective effects of this compound on the development of type 1 diabetes were evaluated in non-obese diabetic (NOD) mice. SPA0355 completely prevented cytokine-induced nitric oxide synthase (iNOS) expression and cytotoxicity in RINm5F cells and isolated islets. The molecular mechanism of SPA0355 inhibition of iNOS expression involves the inhibition of nuclear factor κB and Janus kinase signal transducer and activator of transcription pathways. The protective effects of SPA0355 against cytokine toxicity were further demonstrated by normal insulin secretion and absence of apoptosis of cytokine-treated islets. In experiments with NOD mice, the occurrence of diabetes was efficiently reduced when the mice were treated with SPA0355. Therefore, SPA0355 might be a valuable treatment option that delays the destruction of pancreatic β cells in type 1 diabetes. Nature Publishing Group 2013-11 2013-11-01 /pmc/articles/PMC3849566/ /pubmed/24176948 http://dx.doi.org/10.1038/emm.2013.109 Text en Copyright © 2013 KSBMB. http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/ |
spellingShingle | Original Article Bae, Ui-Jin Song, Mi-Young Jang, Hyun-Young Jin Gim, Hyo Ryu, Jae-Ha Lee, Sang-Myeong Jeon, Raok Park, Byung-Hyun The efficacy of SPA0355 in protecting β cells in isolated pancreatic islets and in a murine experimental model of type 1 diabetes |
title | The efficacy of SPA0355 in protecting β cells in isolated pancreatic islets and in a murine experimental model of type 1 diabetes |
title_full | The efficacy of SPA0355 in protecting β cells in isolated pancreatic islets and in a murine experimental model of type 1 diabetes |
title_fullStr | The efficacy of SPA0355 in protecting β cells in isolated pancreatic islets and in a murine experimental model of type 1 diabetes |
title_full_unstemmed | The efficacy of SPA0355 in protecting β cells in isolated pancreatic islets and in a murine experimental model of type 1 diabetes |
title_short | The efficacy of SPA0355 in protecting β cells in isolated pancreatic islets and in a murine experimental model of type 1 diabetes |
title_sort | efficacy of spa0355 in protecting β cells in isolated pancreatic islets and in a murine experimental model of type 1 diabetes |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3849566/ https://www.ncbi.nlm.nih.gov/pubmed/24176948 http://dx.doi.org/10.1038/emm.2013.109 |
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