Effect of Wnt Signaling on the Differentiation of Islet β-Cells from Adipose-Derived Stem Cells

The Wnt signaling is critical for pancreatic development and islet function; however, its precise effects on the development and function of the beta-cells remain controversial. Here we examined mRNA and protein expression of components of the Wnt signaling throughout the differentiation of islet beta-cells fromadipose-derived stemcells (ADSCs). After induction, ADSCs expressed markers of beta-cells, including the insulin, PDX1, and glucagon genes, and the PDX1, CK19, nestin, insulin, and C-peptide proteins, indicating their successful differentiation. Compared with pancreatic adult stem cells (PASCs), the quantities of insulin, GLUT2, and Irs2 mRNA decreased, whereas Gcg, Gck, and Irs1 mRNA increased. Over time, during differentiation, insulin mRNA and protein expression increased, Gcg and Gck mRNA expression increased, Irs1 mRNA expression decreased and then increased, and Irs2 mRNA increased and then decreased (all p < 0.05). The expression of Dvl-2, LRP5, and GSK3 beta mRNA as well as the Dvl- 2, GSK3 beta, and p- GSK3 beta proteins also increased (p < 0.05). Expression of TCF7L2 (6-10 d) and beta-catenin mRNA as well as the beta-catenin protein increased but not significantly (p > 0.05). Our results indicate that the Wnt signaling is activated during ADSC differentiation into islet beta-cells, but there was no obvious enrichment of nonphosphorylated beta-catenin protein.