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

As mitochondrial metabolism is a major determinant of β-cell insulin secretion, mitochondrial dysfunction underlies β-cell failure and type 2 diabetes mellitus progression. An algal polysaccharide of , 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 (HO)-induced β-cell failure in MIN6 cells and islets. SFG significantly promoted the HO-inhibited proliferation in the cells and ameliorated their senescence, and potentiated β-cell function by regulating β-cell identity and the insulin exocytosis-related genes and proteins in HO-induced β-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-α pathway activation and upregulated the downstream Nrf2 and Tfam. Taken together, the results show that SFG attenuates HO-induced β-cell failure by improving mitochondrial function SIRT1-PGC1-α signaling pathway activation. Therefore, SFG is implicated as a potential agent for treating pancreatic β-cell failure.