在VGLUT2或Sim1细胞中的生长激素受体调节血糖和胰岛素敏感性
Mariana R Tavares1, Willian O Dos Santos1, Andressa G Amaral1
1Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo 05508-000, Brazil.
概括
增长激素受体在特定大脑神经元中的信号传递改善了葡萄糖控制. 切除这些细胞中的生长激素受体会提高胰岛素敏感性,降低血糖水平.
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 代谢调节
- 葡萄糖的恒常性 葡萄糖的恒常性
背景情况:
- 增长激素 (GH) 显著影响葡萄糖平衡,过度分泌与胰岛素抵抗和糖尿病有关.
- GH通过GH受体 (GHR) 发挥其作用.
- 特定的神经元群体在调节代谢过程中发挥作用.
研究的目的:
- 调查GHR信号在VGLUT2表达型谷氨酸神经元中对葡萄糖代谢的作用.
- 为了确定特定的神经元亚型,调解GH对葡萄糖平衡的作用.
主要方法:
- 在VGLUT2-表达细胞 (VGLUT2∆GHR) 中产生和分析了GHR废除的小鼠.
- 分析代谢参数,包括身体成分,血糖,耐葡萄糖和胰岛素敏感性.
- 在Sim1表达细胞 (Sim1∆GHR小鼠) 中研究了GHR无活性.
- 评估肝脏胰岛素敏感性和内源性葡萄糖生产.
- 检查了对外源性GH诱导糖尿病的保护以及药理干预的效果.
主要成果:
- 在VGLUT2表达细胞中的GHR切除可以减少瘦体质量,但不能减少脂肪.
- VGLUT2∆GHR小鼠显示血糖降低,改善葡萄糖耐受性和增强胰岛素敏感性.
- 在Sim1表达神经元中的GHR无活化重现了这些代谢改善.
- Sim1∆GHR小鼠表现出降低葡萄糖的生产和改善肝脏胰岛素敏感性.
- 这些小鼠被保护免受GH的急性,但不是慢性,糖尿病效应.
- 大脑ATP敏感通道的激活使Sim1小鼠的血糖正常化.
结论:
- 在VGLUT2/Sim1表达神经元中缺少GHR信号导致血糖持续降低,并改善肝脏胰岛素敏感性.
- 中央葡萄糖感应机制与观察到的血糖降低有关.
- 这项研究揭示了GHR信号在调节大脑内的葡萄糖平衡中的新机制.
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