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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...

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Autores principales: Juang, Jyuhn-Huarng, Van, Yang-Hau, Kuo, Chien-Hung, Lin, Mei-Yin, Liu, Ying-Hsiu, Chang, Han-Ying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2014
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.
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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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