Fibroblast Growth Factor 19 (FGF-19) Expression in Glycoresistant Human Umbilical Cord Mesenchymal Stem Cells (ghUC-MSCs) and Its Regulatory Effect on Glucose Metabolism in Insulin-Resistant Hepatocytes.

Objective: This study aimed to investigate the expression of FGF-19 in human umbilical cord mesenchymal stem cells (hUC-MSCs) after high-glucose culture. Furthermore, its regulatory effect on glucose metabolism in induced insulin-resistant hepatocytes (IIRHCs) and the underlying mechanism were investigated. Methods: ghUC-MSCs were obtained via acclimation culture of hUC-MSCs with 2 g/L glucose medium. Immunofluorescence and ELISA were used to detect FGF-19 expression in ghUC-MSCs. GOD-POD, RT-qPCR and Western blot techniques were used to determine the effects of ghUC-MSCs and FGF-19 on glucose uptake and insulin sensitivity in IIRHCs. Results: The ghUC-MSCs efficiently expressed FGF-19 and promoted glucose uptake in IIRHCs. However, the FGF-19 receptor inhibitor (FGFR4-IN) significantly reduced ghUC-MSCs-induced glucose uptake in IIRHCs. Notably, FGF-19 and ghUC-MSCs did not influence the effect of insulin on glucose uptake in IIRHCs. Besides, ghUC-MSCs did not significantly increase the phosphorylation level of insulin receptors. Furthermore, ghUC-MSCs and ghUC-MSCs plus FGFR4-IN significantly increased the expression of Glucose Transporter 1 (GLUT1) in IIRHCs. Additionally, ghUC-MSCs significantly increased AKT/ERK phosphorylation in IIRHCs, but this effect was negated by FGFR4-IN1. Conclusion: ghUC-MSCs can efficiently express FGF-19. ghUC-MSCs and FGF-19 can regulate hepatocyte glucose metabolism. However, this regulatory effect is not dependent on the insulin signaling pathway.