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...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2014-01-01
|
| Series: | International Journal of Endocrinology |
| Online Access: | http://dx.doi.org/10.1155/2014/435481 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832560350410571776 |
|---|---|
| author | Jyuhn-Huarng Juang Yang-Hau Van Chien-Hung Kuo Mei-Yin Lin Ying-Hsiu Liu Han-Ying Chang |
| author_facet | Jyuhn-Huarng Juang Yang-Hau Van Chien-Hung Kuo Mei-Yin Lin Ying-Hsiu Liu Han-Ying Chang |
| author_sort | Jyuhn-Huarng Juang |
| collection | DOAJ |
| 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 | Article |
| id | doaj-art-d75c8036dd6c416282c909d95296852f |
| institution | Kabale University |
| issn | 1687-8337 1687-8345 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Endocrinology |
| spelling | doaj-art-d75c8036dd6c416282c909d95296852f2025-02-03T01:27:51ZengWileyInternational Journal of Endocrinology1687-83371687-83452014-01-01201410.1155/2014/435481435481Prevention and Reversal of Diabetes by All-Trans Retinoid Acid and Exendin-4 in NOD MiceJyuhn-Huarng Juang0Yang-Hau Van1Chien-Hung Kuo2Mei-Yin Lin3Ying-Hsiu Liu4Han-Ying Chang5Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung University and Chang Gung Memorial Hospital, 5 Fu-Shin Street, Kweishan, Taoyuan 333, TaiwanDivision of Pediatric Endocrinology, Department of Pediatrics, Chang Gung Memorial Hospital, 5 Fu-Shin Street, Kweishan, Taoyuan 333, TaiwanBiomedical Technology and Device Research Laboratories, Industrial Technology Research Institute of Taiwan, 195 Sec. 4, Chung Hsing Road, Chutung, Hsinchu 31040, TaiwanDivision of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung University and Chang Gung Memorial Hospital, 5 Fu-Shin Street, Kweishan, Taoyuan 333, TaiwanDivision of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung University and Chang Gung Memorial Hospital, 5 Fu-Shin Street, Kweishan, Taoyuan 333, TaiwanDivision of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung University and Chang Gung Memorial Hospital, 5 Fu-Shin Street, Kweishan, Taoyuan 333, TaiwanIt 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.http://dx.doi.org/10.1155/2014/435481 |
| spellingShingle | Jyuhn-Huarng Juang Yang-Hau Van Chien-Hung Kuo Mei-Yin Lin Ying-Hsiu Liu Han-Ying Chang Prevention and Reversal of Diabetes by All-Trans Retinoid Acid and Exendin-4 in NOD Mice International Journal of Endocrinology |
| 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 |
| url | http://dx.doi.org/10.1155/2014/435481 |
| work_keys_str_mv | AT jyuhnhuarngjuang preventionandreversalofdiabetesbyalltransretinoidacidandexendin4innodmice AT yanghauvan preventionandreversalofdiabetesbyalltransretinoidacidandexendin4innodmice AT chienhungkuo preventionandreversalofdiabetesbyalltransretinoidacidandexendin4innodmice AT meiyinlin preventionandreversalofdiabetesbyalltransretinoidacidandexendin4innodmice AT yinghsiuliu preventionandreversalofdiabetesbyalltransretinoidacidandexendin4innodmice AT hanyingchang preventionandreversalofdiabetesbyalltransretinoidacidandexendin4innodmice |