Ghrelin regulates GLP-1 production through mTOR signaling in L cells
Ghrelin regulates GLP-1 production through mTOR signaling in L cells
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Ghrelin 通过 L 细胞中的 mTOR 信号传导调节 GLP-1 的产生
DOI：
10.1016/j.mce.2015.08.016
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发表时间：
2015
影响因子：
4.1
通讯作者：
Zhang Weizhen
中科院分区：
文献类型：
--
作者：
Xu Geyang;Hong Xiaosi;Tang Hong;Jiang Sushi;Liu Fenting;Shen Zhemin;Li Ziru;Zhang Weizhen
胰高血糖素样肽（GLP-1）是一种肠促胰岛素，在L细胞中产生，并在进食时释放，具有促进胰岛素分泌和降低血糖的功能。Ghrelin是一种对葡萄糖稳态至关重要的食欲激素。Ghrelin改变GLP-1产生的分子机制在很大程度上仍然未知。在这里，我们发现ghrelin通过mTOR信号传导减弱GLP-1的产生。在GHSR 1a敲除小鼠中，回肠mTOR信号传导、胰高血糖素原和循环GLP-1显著增加。D-Lys-3-GHRP-6对GHSR 1a的拮抗作用增加了STC-1细胞中GLP-1的合成和释放。用ghrelin处理STC-1细胞减少GLP-1的产生。这种效应与mTOR信号传导的显著抑制相关。生长素释放肽的过表达抑制胰高血糖素原启动子活性和GLP-1的产生。通过mTOR siRNA抑制mTOR活性阻断了STC-1细胞中D-Lys-3-GHRP-6诱导的GLP-1产生。我们的研究结果表明，mTOR信号介导的生长激素释放肽对GLP-1的生产的抑制作用。
Glucagon-like peptide (GLP-1), an intestinal incretin produced in L-cells and released in response to meal intake, functions to promote insulin secretion and to decrease plasma glucose. Ghrelin is an orexigenic hormone critical for glucose homeostasis. The molecular mechanism by which ghrelin alters GLP-1 production remains largely unknown. Here we showed that ghrelin attenuates GLP-1 production through mTOR signaling. In GHSR1a null mice, ileal mTOR signaling, proglucagon and circulating GLP-1 were significantly increased. Antagonism of the GHSR1a by D-Lys-3-GHRP-6 increased GLP-1 synthesis and release in STC-1 cells. Treatment of STC-1 cells with ghrelin decreased the production of GLP-1. This effect was associated with a significant inhibition of mTOR signaling. Overexpression of ghrelin inhibited proglucagon promoter activity and GLP-1 production. Inhibition of mTOR activity by mTOR siRNA blocked D-Lys-3-GHRP-6 induced GLP-1 production in STC-1 cells. Our results suggest that mTOR signaling mediates the inhibitory effect of ghrelin on GLP-1 production.