Irisin alleviates FFA induced β-cell insulin resistance and inflammatory response through activating PI3K/AKT/FOXO1 signaling pathway

Purpose Type 2 diabetes mellitus is characterized by insulin resistance and beta-cell dysfunction. Elevated free fatty acids-induced lipotoxicity may play a vital role in the pathogenesis of beta-cell insulin resistance. Exercise-stimulated myokine irisin has been reported to be closely related to T2DM. However, its function on beta-cell insulin signaling and the underlying mechanisms are only partially elucidated as yet. Methods High-fat diet-fed C57BL/6J mice and palmitic acid-treated MIN6 cell models were utilized as lipotoxic models. Factors associated with beta-cell insulin signaling transduction and inflammatory responses were assessed in these models. Furthermore, the role of irisin in beta-cells and the underlying mechanisms were also explored. Results Irisin effectively decreased lipid levels in HFD mice, enhanced glucose-stimulated insulin secretion and nullified the expressions of inflammatory cytokines in vivo and in vitro experiments. Moreover, irisin improved PI3K/AKT insulin signaling pathway and inhibited TLR4/NF-kappa B inflammatory signaling pathway in both islets of HFD mice and PA-treated MIN6 cells. Mechanistic analysis indicated that FOXO1 might serve as a bridge between the two pathways. Conclusion Irisin alleviates lipotoxicity-induced beta-cell insulin resistance and inflammatory response through the activation of PI3K/AKT/FOXO1 signaling pathways and the inhibition of TLR4/NF-kappa B signaling pathways. Irisin might provide a novel therapeutic strategy for T2DM.

Automated summary

Research shows that irisin effectively decreases lipid levels in HFD mice, enhances glucose-stimulated insulin secretion, and inhibits the expressions of inflammatory cytokines both in vivo and in vitro experiments. Furthermore, irisin improves the PI3K/AKT insulin signaling pathway and inhibits the TLR4/NF-kappa B inflammatory signaling pathway.