Sulfated fuco-manno-glucuronogalactan alleviates pancreatic beta cell senescence via PI3K/AKT/FoxO1 pathway
Authors:
Wenjing Zhang a 1, Nan Wu a 1, Hong Wang a, Genxiang Mao c, Xiaojun Yan d, Fuming Zhang e, Robert J. Linhardt e f, Weihua Jin b, Jiaqiang Zhou a
Affiliation:
aDepartment of Endocrinology and Metabolism, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China
bCollege of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, China
cZhejiang Provincial Key Lab of Geriatrics, Department of Geriatrics, Zhejiang Hospital, Hangzhou 310013, China
dMarine Science and Technical College, Zhejiang Ocean University, Zhoushan 316022, China
eDepartment of Chemical and Biological Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA
fDepartment of Biological Science, Departments of Chemistry and Chemical Biology and Biomedical Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, US
Description:
Appearance of senescent beta cells in the pancreas leads to the onset of type 2 diabetes (T2D). The structural analysis of a sulfated fuco-manno-glucuronogalactan (SFGG) indicated SFGG had the backbones of interspersing 1, 3-linked β-D-GlcpA residues, 1, 4-linked α-D-Galp residues, and alternating 1, 2-linked α-D-Manp residues and 1, 4-linked β-D-GlcpA residues, sulfated at C6 of Man residues, C2/C3/C4 of Fuc residues and C3/C6 of Gal residues, and branched at C3 of Man residues. SFGG effectively alleviated senescence-related phenotypes in vitro and in vivo, including cell cycle, senescence-associated β-galactosidase, DNA damage and senescence-associated secretory phenotype (SASP) -associated cytokines and hall markers of senescence. SFGG also alleviated beta cell dysfunction in insulin synthesis and glucose-stimulated insulin secretion. Mechanistically, SFGG attenuated senescence and improved beta cell function via PI3K/AKT/FoxO1 signaling pathway. Therefore, SFGG could be used for beta cell senescence treatment and alleviation of the progression of T2D.
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