氨酸通过直接调节α细胞cAMP来抑制胰腺小岛的葡萄糖分泌
Emily R Knuth1, Hannah R Foster1, Erli Jin1
1Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, University of Wisconsin-Madison, Madison, WI 53705, USA.
氨基酸白氨酸通过降低cAMP水平来抑制胰腺α细胞释放的葡萄糖. 这种内在的α细胞效应,依赖于谷氨酸脱酶,影响血糖恒温.
科学领域:
- 内分泌学 在内分泌学.
- 代谢调节 代谢调节 代谢调节 代谢调节
- 细胞生理学 细胞生理学
背景情况:
- 胰腺小岛调节血糖平衡.
- 阿尔法细胞的葡萄糖分泌是至关重要的,但其代谢调节的理解不足.
研究的目的:
- 调查生理性白水平在α细胞葡萄糖调节中的作用.
- 阐明白氨酸对阿尔法细胞影响的机制.
主要方法:
- 产生了GcgCreERT:CAMPER和GcCreERT:GCaMP6s小鼠,用于对α细胞cAMP和Ca2+的动态测量.
- 利用小岛外试验来同时测量葡萄糖和胰岛素释放.
- 与葡萄糖,氨酸类似物 (BCH,KIC) 和线粒体燃料相比较氨酸的效果,同时抑制对神经信号传递.
主要成果:
- 氨酸以剂量依赖的方式抑制了氨基酸刺激的葡萄糖分泌.
- 氨酸在生理度下降了α细胞cAMP,但没有影响Ca2+.
- 氨酸的作用是阿尔法细胞固有的,依赖于谷氨酸脱酶和线粒体透症,在老鼠和人类小岛上观察到.
结论:
- 生理性白水平在阿尔法细胞代谢调节中起着重要作用.
- 氨酸通过通过谷氨酸脱酶减少α细胞cAMP,本质上抑制葡萄糖分泌.
- 线粒体透症调解了白和葡萄糖的葡萄糖稳定作用,共同降低了α细胞的度.
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