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丁酸盐作为基因素脱乙酶抑制剂起作用,保护胰腺β细胞免受IL-1β诱导的功能障碍

Signe Schultz Pedersen¹, Lars Roed Ingerslev², Mathias Olsen¹

¹Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.

The FEBS journal

|November 20, 2023

概括

丁酸盐通过抑制素脱乙酶3 (HDAC3) 来保护胰腺β细胞免受炎症. 这种机制使葡萄糖平衡正常化,为2型糖尿病 (T2D) 提供了潜在的治疗方法.

科学领域:

内分泌学在内分泌学.
代谢过程中的代谢.
分子生物学分子生物学

背景情况:

肠道微生物代谢物丁酸盐在2型糖尿病 (T2D) 管理方面显示出前景.
丁酸盐保护胰腺β细胞免受细胞因子诱导的功能障碍.
低度炎症,模仿T2D条件,损害β细胞功能.

研究的目的:

阐明丁酸盐保护胰腺β细胞的分子机制.
为了研究基因组脱乙酶3 (HDAC3) 和基因组乙化在丁酸盐保护作用中的作用.
确定丁酸盐对与炎症和荷尔蒙分泌相关的基因表达的影响.

主要方法:

在小鼠的胰腺小岛中,暴露于IL-1β (IL-1β) 以诱导炎症.
评估了酸盐,HDAC3抑制剂和FFAR2/3激动剂对β细胞功能的影响.
测量了基因组脱乙酶活性和基因组H3/H4乙化水平.
使用ChIP-seq.进行了对H3K27ac的全基因组分析.
基因本体学分析确定了受影响的生物途径.

主要成果:

一种HDAC3抑制剂模仿了丁酸盐对IL-1β受损胰岛素分泌和含量的保护作用.
然而,FFAR2/3激动剂并没有恢复β细胞功能.
丁酸盐抑制了HDAC活性,增加了基因组H3和H4乙化.
丁酸盐调节了H3K27ac水平在参与激素分泌和炎症的基因促进者.
丁酸盐改变了与MAPK信号传递,激素分泌,分化和细胞复制相关的基因附近的H3K27ac.

结论:

丁酸盐通过抑制HDAC来防止IL-1β诱导的胰腺小岛功能障碍.
特定基因位置的H3K27ac模式的变化介导着丁酸盐的有益作用.
抑制HDAC3和随后的表观遗传修饰是Butyrate在T2D治疗潜力的关键机制.

关键词:

贝塔细胞是贝塔细胞的组成部分.黄油酸盐黄油酸盐是一种基因素乙化基因素乙化基因素乙化希斯顿脱乙酶的使用胰岛素分泌的胰岛素分泌.

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