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

Figure 10

Schematic diagram depicting proposed mechanism for the Wnt signaling pathway activation during differentiation of ADSCs into insulin-producing cells. ADSCs, in the induction of islet β-cells medium, initiate islet β-cells differentiation. Islet β-cells commitment is linked to the stimulation of the canonical Wnt pathway that sequentially involves the following: the Wnt ligand combines with the Frizzled (Fz) and LRP5/6 receptors. Fz then recruits Dvl, leading to phosphorylation at the LRP5/6 intracellular terminal. The phosphorylation of GSK3β leads to the inactivation of a cytoplasmic complex composed of CK1, Axin, APC, and GSK3β and detachment of β-catenin phosphorylation from the complex. These events result in the increase of β-catenin mRNA, but it was not obvious in β-catenin protein (possibly undergoing posttranscriptional modifications, actions of miRNA, etc.). The β-catenin stabilization activates the islet β-cells marker insulin in the transcriptional and translational levels. DKK-1 is a secreted Wnt antagonist that may be used as a drug to inhibit Wnt signal. CK1, casein kinase 1; DKK-1, Dickkopf 1; Dvl, dishevelled; GSK3β, glycogen synthase kinase 3β; LRP5/6, low-density lipoprotein receptor-related protein 5/6; TCF, T-cell factor.