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Prevention and Reversal of Diabetes by All-Trans Retinoid Acid and Exendin-4 in NOD Mice
It has been shown that all-trans retinoid acid (ATRA) hinders the development of autoimmune diabetes by inducing immune tolerance status. Meanwhile, exendin-4 increases beta-cell function and mass. Thus, we hypothesized that ATRA and exendin-4 combination therapy would prevent and reverse autoimmune...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi Publishing Corporation
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4065745/ https://www.ncbi.nlm.nih.gov/pubmed/24995016 http://dx.doi.org/10.1155/2014/435481 |
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author | Juang, Jyuhn-Huarng Van, Yang-Hau Kuo, Chien-Hung Lin, Mei-Yin Liu, Ying-Hsiu Chang, Han-Ying |
author_facet | Juang, Jyuhn-Huarng Van, Yang-Hau Kuo, Chien-Hung Lin, Mei-Yin Liu, Ying-Hsiu Chang, Han-Ying |
author_sort | Juang, Jyuhn-Huarng |
collection | PubMed |
description | It has been shown that all-trans retinoid acid (ATRA) hinders the development of autoimmune diabetes by inducing immune tolerance status. Meanwhile, exendin-4 increases beta-cell function and mass. Thus, we hypothesized that ATRA and exendin-4 combination therapy would prevent and reverse autoimmune diabetes. NOD/scid mice were intravenously transferred with splenocytes isolated from 12-week-old female NOD mice. After adoptive transfer, mice were treated with vehicle, ATRA (0.5 mg/mouse intraperitoneally every other day), exendin-4 (3 μg/kg subcutaneously twice daily), or combination for 6 weeks. Compared with vehicle, ATRA (P = 0.022) and ATRA plus exendin-4 (P = 0.013) treatment delayed the onset of diabetes. The pancreatic insulin content in mice treated with ATRA (P = 0.013) and exendin-4 (P < 0.02) was significantly higher than that of control mice. All but one spontaneous diabetic NOD mouse treated with ATRA and/or exendin-4 remained persistent hyperglycemic. ATRA and/or exendin-4 treatment did not alter their blood glucose levels and survival. Our results indicate that, before the onset of autoimmune diabetes, ATRA and exendin-4 treatment alone preserves pancreatic beta cells; ATRA and ATRA plus exendin-4 treatment delays the onset of autoimmune diabetes. However, after the onset of autoimmune diabetes, ATRA and/or exendin-4 treatment is unable to reverse hyperglycemia or improve survival. |
format | Online Article Text |
id | pubmed-4065745 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-40657452014-07-03 Prevention and Reversal of Diabetes by All-Trans Retinoid Acid and Exendin-4 in NOD Mice Juang, Jyuhn-Huarng Van, Yang-Hau Kuo, Chien-Hung Lin, Mei-Yin Liu, Ying-Hsiu Chang, Han-Ying Int J Endocrinol Research Article It has been shown that all-trans retinoid acid (ATRA) hinders the development of autoimmune diabetes by inducing immune tolerance status. Meanwhile, exendin-4 increases beta-cell function and mass. Thus, we hypothesized that ATRA and exendin-4 combination therapy would prevent and reverse autoimmune diabetes. NOD/scid mice were intravenously transferred with splenocytes isolated from 12-week-old female NOD mice. After adoptive transfer, mice were treated with vehicle, ATRA (0.5 mg/mouse intraperitoneally every other day), exendin-4 (3 μg/kg subcutaneously twice daily), or combination for 6 weeks. Compared with vehicle, ATRA (P = 0.022) and ATRA plus exendin-4 (P = 0.013) treatment delayed the onset of diabetes. The pancreatic insulin content in mice treated with ATRA (P = 0.013) and exendin-4 (P < 0.02) was significantly higher than that of control mice. All but one spontaneous diabetic NOD mouse treated with ATRA and/or exendin-4 remained persistent hyperglycemic. ATRA and/or exendin-4 treatment did not alter their blood glucose levels and survival. Our results indicate that, before the onset of autoimmune diabetes, ATRA and exendin-4 treatment alone preserves pancreatic beta cells; ATRA and ATRA plus exendin-4 treatment delays the onset of autoimmune diabetes. However, after the onset of autoimmune diabetes, ATRA and/or exendin-4 treatment is unable to reverse hyperglycemia or improve survival. Hindawi Publishing Corporation 2014 2014-06-03 /pmc/articles/PMC4065745/ /pubmed/24995016 http://dx.doi.org/10.1155/2014/435481 Text en Copyright © 2014 Jyuhn-Huarng Juang et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Juang, Jyuhn-Huarng Van, Yang-Hau Kuo, Chien-Hung Lin, Mei-Yin Liu, Ying-Hsiu Chang, Han-Ying Prevention and Reversal of Diabetes by All-Trans Retinoid Acid and Exendin-4 in NOD Mice |
title | Prevention and Reversal of Diabetes by All-Trans Retinoid Acid and Exendin-4 in NOD Mice |
title_full | Prevention and Reversal of Diabetes by All-Trans Retinoid Acid and Exendin-4 in NOD Mice |
title_fullStr | Prevention and Reversal of Diabetes by All-Trans Retinoid Acid and Exendin-4 in NOD Mice |
title_full_unstemmed | Prevention and Reversal of Diabetes by All-Trans Retinoid Acid and Exendin-4 in NOD Mice |
title_short | Prevention and Reversal of Diabetes by All-Trans Retinoid Acid and Exendin-4 in NOD Mice |
title_sort | prevention and reversal of diabetes by all-trans retinoid acid and exendin-4 in nod mice |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4065745/ https://www.ncbi.nlm.nih.gov/pubmed/24995016 http://dx.doi.org/10.1155/2014/435481 |
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