AUTHOR=Wu Nan , Jin Weihua , Zhao Yuchen , Wang Hong , He Sunyue , Zhang Wenjing , Zhou Jiaqiang 

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

JOURNAL=Frontiers in Endocrinology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2022.881256

DOI=10.3389/fendo.2022.881256

ISSN=1664-2392

ABSTRACT=<p>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 <italic>Laminaria japonica</italic>, 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 (H<sub>2</sub>O<sub>2</sub>)-induced β-cell failure in MIN6 cells and islets. SFG significantly promoted the H<sub>2</sub>O<sub>2</sub>-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 H<sub>2</sub>O<sub>2</sub>-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 H<sub>2</sub>O<sub>2</sub>-induced β-cell failure by improving mitochondrial function <italic>via</italic> SIRT1–PGC1-α signaling pathway activation. Therefore, SFG is implicated as a potential agent for treating pancreatic β-cell failure.</p>