Sulfated Fucogalactan From Laminaria Japonica Ameliorates β-Cell Failure by Attenuating Mitochondrial Dysfunction via SIRT1-PGC1-α Signaling Pathway Activation

As mitochondrial metabolism is a major determinant of beta-cell insulin secretion, mitochondrial dysfunction underlies beta-cell failure and type 2 diabetes mellitus progression. An algal polysaccharide of Laminaria japonica, sulfated fucogalactan (SFG) displays various pharmacological effects in a variety of conditions, including metabolic disease. We investigated the protective effects of SFG against hydrogen peroxide (H2O2)-induced beta-cell failure in MIN6 cells and islets. SFG significantly promoted the H2O2-inhibited proliferation in the cells and ameliorated their senescence, and potentiated beta-cell function by regulating beta-cell identity and the insulin exocytosis-related genes and proteins in H2O2-induced beta-cells. SFG also attenuated mitochondrial dysfunction, including alterations in ATP content, mitochondrial respiratory chain genes and proteins expression, and reactive oxygen species and superoxide dismutase levels. Furthermore, SFG resulted in SIRT1-PGC1-alpha pathway activation and upregulated the downstream Nrf2 and Tfam. Taken together, the results show that SFG attenuates H2O2-induced beta-cell failure by improving mitochondrial function via SIRT1-PGC1-alpha signaling pathway activation. Therefore, SFG is implicated as a potential agent for treating pancreatic beta-cell failure.

Automated summary

Sulfated fucogalactan (SFG), an algal polysaccharide, protects beta-cell function by improving mitochondrial function through activation of the SIRT1-PGC1-alpha signaling pathway.