衰老
福克斯O1
蛋白激酶B
化学
PI3K/AKT/mTOR通路
生物化学
表型
细胞生物学
信号转导
内分泌学
生物
基因
作者
Wenjing Zhang,Nan Wu,Hong Wang,Genxiang Mao,Yan Xin,Fuming Zhang,Robert J. Linhardt,Weihua Jin,Jiaheng Zhou
标识
DOI:10.1016/j.ijbiomac.2023.123846
摘要
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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