Effect of retinoic acid on type I diabetes: Streptozotocin-induced rat model

ABSTRACT

To evaluate the effect of all trans retinoic acid [atRA] on differentiation/transdifferentiation of pancreatic duct/acinar cells into insulin secreting beta-cells in diabetic rats. 64 adult male rats divided into four groups. Normal control, diabetic control, atRA-I diabetic rats treated with atRA [0.1 mg/kg/day, subcutaneously] and atRA-II diabetic rats treated with atRA [2.5 mg/kg/day, subcutaneously] for 1, 2 and 4 weeks. The levels of glucose and insulin were measured. Histopathological, immunohistochemical examination of pancreas and RT-PCR of insulin mRNA were done. atRA led to an improvement in the level of glucose and insulin in both doses and at the different time points when compared with diabetic control. Histopathological examination of the pancreas revealed that atRA in both doses and at different time points nearly restored the normal appearance of the islets of Langerhans. Interestingly, some islets of Langerhans were found closely related to the interlobular ducts and the acinar epithelium. Mitotic figures were observed in the epithelium of the interlobular ducts and acinar cells and inside the islets of Langerhans especially with high dose. The immunohistochemical revealed strong insulin-immunoreactivity in the cytoplasm of the beta-cells and in the cytoplasm of the isolated cells which are closely related to the acini. Also, insulin mRNA expression showed dense band illumination similar to normal control. Retinoic acid may induced significant increase in insulin level and its mRNA, decrease glucose level and increased beta-cells regeneration through increased pancreatic duct and/or acinar cells differentian/transdifferentiation and increased proliferation of fbeta-cells in diabetic rats