在AVP神经元中的Tmem117调节了对低血糖的反调节反应
Sevasti Gaspari1, Gwenaël Labouèbe1, Alexandre Picard1
1Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland.
EMBO reports
|June 14, 2023
概括
该研究确定Tmem117在下丘脑血管压迫神经元中对于调节对低血糖的逆调节反应至关重要. 它的失活促进了血管压素和葡萄糖分泌,影响了葡萄糖平衡.
科学领域:
- 神经内分泌学神经内分泌学
- 代谢调节 代谢调节 代谢调节
- 细胞应激反应的应激反应
背景情况:
- 对低血糖的反调节反应 (CRR) 对大脑葡萄糖供应至关重要,由感知葡萄糖的神经元协调.
- 在CRR中涉及的精确机制和神经元群体仍然不完全理解.
- 脑下垂体Tmem117被确定为CRR的潜在调节者.
研究的目的:
- 为了研究下丘脑Tmem117在低血糖的反调节反应中的作用.
- 为了确定Tmem117在血管压素大细胞神经元中失活的细胞和生理后果.
主要方法:
- 在血管压素神经元中Tmem117的遗传失活.
- 血管压素神经元的体外电生理学.
- 在现场杂交和体内成像.
- 测量血管压素和葡萄糖分泌.
- 评估内等质网膜 (ER) 应激和反应性氧物种 (ROS) 生产.
主要成果:
- Tmem117在下丘脑血管压力中表达,在巨细胞神经元中.
- Tmem117的失活会增加低血糖引起的血管压缩素分泌,导致雄性小鼠的葡萄糖分泌量升高.
- 在雌性小鼠中,Tmem117无活化的对血管压素分泌的影响是依赖雌性性周期阶段的.
- Tmem117的失活不会改变葡萄糖感应特性,但会增加ER压力,ROS产量和血管压素神经元中的细胞内,增强血管压素的产生和分泌.
结论:
- 血管压迫神经元中的Tmem117是低血糖期间葡萄糖分泌的生理调节者.
- 血管压素大细胞神经元在对低血糖的协调激素反应中发挥着重要作用.
- Tmem117通过涉及ER压力和信号传递的机制调节血管压素神经元活动和分泌.
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