Oral Administration of Synthetic Retinoid Am80 Inhibits the Development of Type 1 Diabetes in Non-obese Diabetic (NOD) Mice

Abstract

Synthetic retinoid Am80 is a potent modulator of the immune system. Am80 is effective in various experimentally induced autoimmune disorders. The purpose of this study is to confirm its effect on non-obese diabetic (NOD) mice, which spontaneously develop autoimmune type 1 diabetes. Am80 was orally administered in feed to 6 NOD mice per group at a dose of 0 (control), 0.1 (low) or 1 (high) mg/kg/d for 19 weeks. During the experiment period, the high urine glucose levels were observed in 33% mice of the control and low Am80 groups, whereas any mouse in the high Am80 group did not show abnormal urine glucose level. Histological examination showed that the average score of insulitis severity in the low Am80 group was similar to that in the control; however in the high Am80 group, the score was significantly reduced compared to that in the control group. Similarly, the severity of lymphocyte infiltration in the submandibular glands showed a tendency to decrease in the high Am80 group, but not in the low Am80 group, compared to the control. These data strongly suggest that the development of type 1 diabetes in NOD mice can be inhibited by oral administration of Am80.