All-trans retinoic acid prevents the development of type 1 diabetes by affecting the levels of interferon gamma and interleukin 4 in streptozotocin-induced murine diabetes model

Abstract

The aim of this study was to explore the molecular mechanism by which all-trans retinoic acid (ATRA) prevents type 1 diabetes mellitus (T1DM). Fifty ICR mice were randomly assigned to three groups: prevention group [N = 20; mice received 10 mg/kg ATRA daily for 5 days and then 60 mg/kg streptozotocin (STZ) for 5 days]; diabetic group (N = 20, mice received 95% sterile peanut oil and 5% dimethyl sulfoxide for 5 days and then 60 mg/kg STZ for 5 days); and control group (N = 10, mice received 95% sterile peanut oil and 5% dimethyl sulfoxide for 5 days and then citrate buffer for 5 days). Blood glucose was measured using blood glucose test strips and serum insulin was measured by radioimmunoassay. Islets cell morphology was assessed by microscopy and ELISA was used to measure the serum levels of interferon gamma (IFN-γ) and interleukin 4 (IL- 4). In the prevention group, blood sugar levels were found to be reduced and serum insulin levels increased compared with the levels in the diabetic group (P < 0.05), indicating that ATRA prevented the STZinduced damage to islet cells. Meanwhile, ATRA was shown to decrease the levels of IFN-γ and increase the levels of IL-4 as well as the IFN-γ/IL-4 ratio in STZ-treated animals (P < 0.05). These findings suggest that ATRA prevents the recurrence of autoimmune insulitis. This study demonstrated that ATRA effectively prevents the progression of T1DM in a murine model of the disease by reducing IFN-γ levels and increasing IL-4 levels.