title: Exendin-4 enhances expression of Neurod1 and Glut2 in insulin-producing cells derived from mouse embryonic stem cells.
abstract: BACKGROUND
  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 β-cell mass and improving β-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.
  
  
  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 β-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 Insulin1 (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.
authors.affiliation: Department of Histology and Embryology, Harbin Medical University, Harbin, China.
authors.forename: Qiaoshi
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Division of Endocrinology, Heilongjiang Provincial Hospital, Harbin, China.
authors.forename: Yuzhi
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Histology and Embryology, Harbin Medical University, Harbin, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Histology and Embryology, Harbin Medical University, Harbin, China.
authors.forename: Zhiyan
authors.initials: Z
authors.lastname: Shan
authors.affiliation: Department of Histology and Embryology, Harbin Medical University, Harbin, China.
authors.forename: Yanshuang
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Histology and Embryology, Harbin Medical University, Harbin, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Lei
keywords: diabetes; embryonic stem cells; exendin-4; insulin-producing cell