Abstract: Objective To investigate the mechanism by which exendin-4 promotes paracrine secretion of cytokines by
adipose-derived stem cells (ADSCs). Methods In vitro cultured SD rat ADSCs (fourth passage) with or without exendin-4
treatment underwent flow cytometry to characterize the surface markers. MTT assay was performed to assess the proliferation
of the cells exposed to different concentrations (0-20 nm/L) of exendin-4, and the paracrine secretion of cytokines (bFGF, VEGF,
HGF, and IGF-1) by the ADSCs was evaluated by qPCR. The changes in the expressions of p-Akt in the cells were analyzed by
Western blotting and qPCR in response to exendin-4 (10 nm/L) with or without exposure to PI3K/Akt inhibitor LY-294002 (50
nm/L); bFGF, VEGF, HGF, and IGF-1 production in the cells were detected using ELISA kits. Results Treatment with exendin-4
for 12 h did not affect the surface marker profile of the ADSCs but promoted the cell proliferation (P<0.05). Exendin-4
significantly increased the mRNA expressions of VEGF, bFGF, HGF, and IGF-1 in a concentration-dependent manner, and 10
nm/L was the optimum concentration (P<0.05). Exendin-4 treatment resulted in significantly increased p-Akt expressions in the
ADSCs, and PI3K/Akt inhibitor not only reversed such effects of exendin-4 on p-Akt but also diminished the exendin-4-
mediated up-regulation of the paracrine cytokines. Conclusion Exendin-4 can concentration-dependently promote the
proliferative and paracrine capacities of ADSCs partially through the PI3K/Akt signaling pathway without affecting the
surface marker profile of the cells.