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在小鼠中,SRSF2对于维持胰腺β细胞的同一性和调节葡萄糖平衡至关重要

Xue You¹, Qian Peng², Wenju Qian²

¹Lin He's Academician Workstation of New Medicine and Clinical Translation in Jining Medical University, Jining Medical University, Jining, China.

Biochimica et biophysica acta. Molecular cell research

|September 12, 2024

概括

拼接因子SRSF2对于胰腺β细胞的存活和功能至关重要. 在小鼠中,它的缺失会导致糖尿病,因为它会损害β细胞的增殖和葡萄糖的稳定性.

科学领域:

内分泌学在内分泌学.
分子生物学分子生物学
细胞生物学细胞生物学

背景情况:

糖尿病与降低β细胞质量和小岛功能障碍有关.
拼接因子SRSF2对于细胞存活至关重要,但其在胰腺β细胞中的作用尚不清楚.

研究的目的:

研究SRSF2在胰腺β细胞存活,增殖和功能中的作用.
为了确定SRSF2删除对葡萄糖平衡和β细胞身份的影响.

主要方法:

生成了一个小鼠模型,SRSF2在β细胞 (SRSF2_KO) 中被专门删除.
进行葡萄糖耐受性测试并评估胰岛素分泌.
利用单细胞RNA测序 (scRNA-seq) 来分析β细胞群和基因表达.
在小岛和细胞系中检查了β细胞的增殖.

主要成果:

在β细胞中SRSF2的缺失导致葡萄糖耐受性受损,胰岛素分泌量减少,岛屿质量减少.
scRNA-seq揭示了未折叠蛋白反应 (UPR) 激活和未分化β细胞的增加,但减少了UPR/ER基因表达和β细胞身份的丧失.
删除SRSF2导致年轻小鼠和细胞系中的β细胞增殖减少.
在SRSF2_KO小鼠中,小鼠在10个月大时就患上了糖尿病.

结论:

SRSF2对于维护β细胞的增殖和功能至关重要.
失去SRSF2会破坏β细胞的身份和功能,导致糖尿病的发展.
通过β细胞的生存和功能,SRSF2在保持葡萄糖平衡中发挥着关键作用.

关键词:

贝塔细胞特异性淘汰赛小鼠在 SRSF2 基金中,减少了小岛群的质量.在 scRNA-seq 分析中,

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