Effect of naringin on the expression of pdx 1 and foxm 1 transcription factors in beta cells of streptozotocin induced diabetic rats

Abstract

Introduction newlineDiabetes is a challenging health problem increasing at an alarming rate. It is characterized by reduction in number and function of beta cells. Though quiescent, beta cells are capable of proliferation and this potential is contemplated in the diabetic research. It is also imperative that the proliferated cells are functionally competent enough to secrete insulin. Pancreatic duodenal homeobox-1 (PDX-1) is a critical transcription factor that binds to promoter region of insulin gene and regulates its expression. Forkhead box M1 (FoxM1) transcription factor is an important regulator of beta cell proliferation and survival. In this background, naringin, a flavanone glycoside reported to possess promising antidiabetic potential is being investigated for its possible role on the expression of PDX-1 and FoxM1 transcription factors in the beta cells of streptozotocin (STZ) induced diabetic rats. newline newlineMethodology newlineDiabetes was induced in male rats using STZ and treated with naringin (100 mg/kg) orally for 4 and 8 weeks. Serum insulin, urea, creatinine and cholesterol levels were measured. Pdx-1, FoxM1 and Insulin mRNA expressions in pancreatic tissue were analyzed. PDX-1 and FoxM1 protein expressions in rat pancreas were analyzed by immunohistochemical and western blot methods. Histopathological and ultrastructural changes in the islets and beta cells were examined. newline newlineResults newlineNaringin administration showed reduction in the fasting glucose level and improvement in the serum insulin level of diabetic animals. Naringin prevented leukocytic infiltration in the pancreas of diabetic rats and recouped the beta cells with adequate secretory granules. Naringin-treated diabetic rats showed significantly increased mRNA expression of Pdx-1, FoxM1 and Insulin genes and increased expression of PDX-1 and FoxM1 transcription factors than the diabetic control animals. These changes were marked in the 8-week naringin-treated diabetic animals. newlineConclusion newlineNaringin was found to be ameliorating diabetes by increasing insulin sec