The effect of all-trans Retinoic acid on the progression of diabetes in NOD mice

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SAT 834-867-Islet Biology
Bench to Bedside
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-841
Sana Hasan*1, Frederick G Hamel2, Ronda Simpson1, Cyrus V Desouza3 and Robert Gerard Bennett4
1University of Nebraska Medical Center, Omaha, 2Omaha VA Med Ctr, Omaha, NE, 3Univ of Nebraska Med Center, Omaha, NE, 4VA Med Ctr, Omaha, NE
Retinoid acid is a Vitamin A metabolite which has been recognized as important immune-potentiating agent due to its modulatory effects on both T and B cells.  A potent derivative of vitamin A is all-trans Retinoic Acid (ATRA).  Recent studies revealed that ATRA can induce immune tolerance that inhibits islet inflammation.   The majority of these studies focused on the prevention of type 1 diabetes with ATRA treatment.  We investigated the effect of oral ATRA treatment on the progression of type 1 diabetes in an NOD model.  We started treatment at 10 weeks, at which point Insulitis has been progressing in this model. Female NOD mice (10 per group) were treated with vehicle (corn oil) or ATRA at 0.6 mg/mouse, 5 days/week for 20 weeks by voluntary oral feeding.  Body weight and random glucose levels were determined weekly, and glucose tolerance test was performed at 10 and 20 weeks.   Baseline random blood glucose (73.7 ± 3.2 mg/dL control vs 80.2± 5.7mg/dL ATRA) and body weight (19.8 ± 0.4 g control vs 18.9 g ± 0.2 g ATRA) were similar in both groups.  Fasting blood glucose significantly decreased with ATRA treatment at week 10 (99.2±17.6 control vs 55.7±10.6 ATRA, p <0.05) and week 20 (125 ±19.9 mg/dL control vs 71.4 ±4.7 mg/dL ATRA, p< 0.05).  ATRA treatment also improved glucose tolerance as determined by OGTT at week 10 (AUC 14.9±2.5 control vs 8.6±1.0 ATRA, p<0.05) and week 20 (21.3±4.1 control vs 13.3±2.10 ATRA, p=0.08).  No significant changes were observed in random blood glucose and body weight during the course of the study.  There was no difference in the percentage of mice that developed type 1 diabetes.  Our preliminary data suggest that glucose lowering effect of ATRA in pre-diabetic NOD mice demonstrates its prospective use for the treatment of type 1 diabetes.

Disclosure: CVD: Consultant, Novo Nordisk, Consultant, Takeda. Nothing to Disclose: SH, FGH, RS, RGB

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