Exendin-4 Enhances Expression Of Neurodl And Glut2 In Insulin-Producing Cells Derived From Mouse Embryonic Stem Cells

Introduction: Stem cells involved cell replacement therapies for type 1 diabetes mellitus is promising, yet time-consuming and inefficient. Exendin-4 is a glucagon-like peptide-1 (GLP-1) receptor agonist which has been reported to possess anti-apoptotic effects, thereby increasing beta-cell mass and improving beta-cell function. The present study aimed to investigate whether exendin-4 would enhance the differentiation of embryonic stem cells into insulin-secreting cells and improve the pancreatic differentiation strategy.Material and methods: R1 embryonic stem cells were treated with different concentrations of exendin-4 and divided into three groups. In the high dosage group (group H), exendin-4 was added at the dosage of 10 nmol/l. In the low dosage group (group L), exendin-4 was added at the dosage of 0.1 nmol/l. Group C was a control. Expression of genes related to the beta-cell phenotype and immunofluorescence staining of insulin and C-peptide were detected.Results: Compared with groups L and C, group H had the highest mRNA expression levels of Isl1, Pdx1, Ngn3, and Insulinl (p < 0.05). Neurod1 and Glut2 only emerged at the final stage of differentiation in group H. Immunofluorescence analysis revealed that exendin-4 upregulated the protein expression of insulin and C-peptide.Conclusions: Exendin-4 remarkably facilitated Neurod1 and Glut2 gene transcription, and was able to induce differentiation of embryonic stem cells into endocrine and insulin-producing cells.