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SSBP3联合调节器是葡萄糖平衡,胰腺岛架构和β细胞身份的必要条件

Eliana Toren¹, Jessica D Kepple¹, Kristen V Coutinho¹

¹Comprehensive Diabetes Center and Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, University of Alabama at Birmingham, Birmingham, AL 35294, USA.

Molecular metabolism

|August 3, 2023

概括

单链DNA结合蛋白3 (SSBP3) 对于胰腺小岛细胞功能和葡萄糖调节至关重要. 失去SSBP3会损害葡萄糖平衡和胰岛素分泌,突出其在维持β细胞身份方面的作用.

科学领域:

内分泌学和新陈代谢学
分子生物学分子生物学
发展生物学发展生物学

背景情况:

转录复合体活动对于胰腺小岛细胞的发育和功能至关重要,特别是对于葡萄糖调节.
岛屿-1 (Isl1) 和其协同调节器LDB1是β细胞的重要转录因子 (TF).
单链DNA结合蛋白3 (SSBP3) 与Isl1和Ldb1相互作用,在体外影响β细胞点基因.

研究的目的:

调查SSBP3在胰腺小岛细胞功能中的体内作用,假设它与Isl1::Ldb1复合体相似.
为了确定SSBP3损失对葡萄糖平衡,β细胞身份和功能的影响.

主要方法:

开发一种新的SSBP3LoxP等位基因小鼠谱系.
构成性 (SSBP3^ΔPanc,SSBP3^ΔIslet) 和可诱导性 (SSBP3^Δβ细胞) SSBP3淘汰模型的生成.
评估葡萄糖耐受性,葡萄糖刺激胰岛素分泌 (GSIS),小岛细胞丰富度,β细胞标记物和RNA-Seq分析.

主要成果:

在SSBP3淘汰赛中,新生儿 (SSBP3^ΔPanc,SSBP3^ΔIslet) 呈现出高血糖症.
岛屿小鼠表现出葡萄糖不耐受性和降低β细胞成熟度标志物 (MafA,Pdx1,UCN3) 与改变的岛屿结构.
成人β细胞 (SSBP3^Δβ细胞) 中诱导的SSBP3删除导致高血糖症,葡萄糖不耐受,减少GSIS,以及包括压力和脱差标记在内的基因表达变化.

结论:

SSBP3对于维持胰腺小岛的身份和功能以及适当的葡萄糖平衡至关重要.
丢失SSBP3会导致岛屿细胞丰度变化和葡萄糖调节受损.
对于GSIS和葡萄糖平衡来说,SSBP3是必需的,部分是通过对Ldb1和Isl1目标基因的共享调节.

关键词:

同调节器是同调节器.糖尿病糖尿病糖尿病基因调节基因调节葡萄糖的恒常性是葡萄糖的恒常性.胰腺小岛是一个胰腺小岛.转录因子是一种转录因子.

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