prevention and reversal of diabetes by all-trans retinoid acid and exendin-4 in nod mice

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ID: 255448
2014
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Abstract
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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Authors Jyuhn-Huarng Juang, Yang-Hau Van, Chien-Hung Kuo, Mei-Yin Lin, Ying-Hsiu Liu, Han-Ying Chang
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Journal zhonghua wei zhong bing ji jiu yi xue
Year 2014
DOI
10.1155/2014/435481
URL
http://dx.doi.org/10.1155/2014/435481
Keywords
clinical endocrinology diseases of the endocrine glands

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