哈贝努拉TCF7L2与尼古丁成与糖尿病有关
Alexander Duncan1,2, Mary P Heyer1, Masago Ishikawa1
1Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Nature
|October 18, 2019
概括
大脑中的糖尿病相关基因Tcf7l2
科学领域:
- 神经科学
- 遗传学
- 内分泌学
背景情况:
- 吸烟与糖尿病的增加有关, 但机制尚不清楚.
- Tcf7l2基因与糖尿病有关.
- 大脑中部哈本 (mHb) 区域在这种联系中的作用是未知的.
研究的目的:
- 调查Tcf7l2在介质哈本 (mHb) 中对尼古丁对葡萄糖代谢的影响的作用.
- 探索连接尼古丁消费,Tcf7l2和类似糖尿病症状的神经通路.
主要方法:
- 在动物mHb中检查Tcf7l2表达.
- 在mHb中抑制TCF7L2信号以评估尼古丁摄入量.
- 在野生型和Tcf7l2突变大鼠中暴露尼古丁后测量血糖,胰岛素和葡萄糖水平.
- 使用病毒追踪来绘制mHb到胰腺的神经连接.
主要成果:
- Tcf7l2在mHb中高度表达,并调节尼古丁乙胆受体.
- 在mHb中抑制TCF7L2增加了尼古丁摄入量.
- 尼古丁通过TCF7L2依赖的mHb刺激来提高血糖.
- 从mHb到胰腺的一条神经通道被确定.
- 与Tcf7l2突变大鼠不同的是,暴露于尼古丁的野生型大鼠显示出改变的葡萄糖平衡.
结论:
- 在mHb中的Tcf7l2调解了尼古丁对哈本-胰腺轴的刺激作用.
- 这一轴将尼古丁成与促进糖尿病的行为联系起来.
- Tcf7l2是尼古丁使用与糖尿病发展之间神经生物学联系的关键调节者.
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