Activation of intestinal olfactory receptor stimulates glucagon-like peptide-1 secretion in enteroendocrine cells and attenuates hyperglycemia in type 2 diabetic mice.
Activation of intestinal olfactory receptor stimulates glucagon-like peptide-1 secretion in enteroendocrine cells and attenuates hyperglycemia in type 2 diabetic mice.
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DOI：
10.1038/s41598-017-14086-5
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发表时间：
2017-10-25
影响因子：
4.6
通讯作者：
Jang HJ
中科院分区：
文献类型：
--
作者：
Kim KS;Lee IS;Kim KH;Park J;Kim Y;Choi JH;Choi JS;Jang HJ
气味剂是非营养物质。然而，它们大量存在于食物、酒和茶中，因此可以在用餐时与其他营养素一起摄入。在这里，我们将重点放在了这些ORs的化学识别能力上，并假设在用餐过程中摄入的气味可能通过激活肠道表达的ORs发挥生理作用。利用人源性肠内分泌L细胞系，我们发现了香叶醇和香茅醛介导的胰高血糖素样肽-1 （GLP-1）分泌的刺激，并阐明了相应的细胞下游信号通路。香叶醇刺激肠内分泌细胞系GLP-1分泌事件是由嗅觉型G蛋白、腺苷酸环化酶激活、细胞内cAMP水平升高和细胞外钙内流介导的。TaqMan qPCR结果显示，在人肠内分泌细胞系和小鼠肠道标本中分别表达了香叶醇和香橼醛对应的两个ORs。在2型糖尿病小鼠模型（db/db）中，口服香叶醇通过增加血浆GLP-1和胰岛素水平来改善葡萄糖稳态。香叶醇的这种促胰岛素作用是GLP-1受体介导的，也是葡萄糖依赖的。本研究表明，在进食过程中，气味化合物可以被肠道表达的ORs识别，从而通过诱导肠道肽的分泌参与葡萄糖稳态。
Odorants are non-nutrients. However, they exist abundantly in foods, wines, and teas, and thus can be ingested along with the other nutrients during a meal. Here, we have focused on the chemical-recognition ability of these ORs and hypothesized that the odorants ingested during a meal may play a physiological role by activating the gut-expressed ORs. Using a human-derived enteroendocrine L cell line, we discovered the geraniol- and citronellal-mediated stimulation of glucagon-like peptide-1 (GLP-1) secretion and elucidated the corresponding cellular downstream signaling pathways. The geraniol-stimulated GLP-1 secretion event in the enteroendocrine cell line was mediated by the olfactory-type G protein, the activation of adenylyl cyclase, increased intracellular cAMP levels, and extracellular calcium influx. TaqMan qPCR demonstrated that two ORs corresponding to geraniol and citronellal were expressed in the human enteroendocrine cell line and in mouse intestinal specimen. In a type 2 diabetes mellitus mouse model (db/db), oral administration of geraniol improved glucose homeostasis by increasing plasma GLP-1 and insulin levels. This insulinotropic action of geraniol was GLP-1 receptor-mediated, and also was glucose-dependent. This study demonstrates that odor compounds can be recognized by gut-expressed ORs during meal ingestion and therefore, participate in the glucose homeostasis by inducing the secretion of gut-peptides.
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影响因子：
11.8
作者：
Griffin CA;Kafadar KA;Pavlath GK
通讯作者：
Pavlath GK
影响因子：
1.7
作者：
Cui, Mei Nu;Yun, Hye-Hyeon;Lee, Jeong-Hwa
通讯作者：
Lee, Jeong-Hwa
影响因子：
4.8
作者：
De Leon, Diva D.;Li, Changhong;Stoffers, Doris A.
通讯作者：
Stoffers, Doris A.
DOI：
10.1073/pnas.0307882100
发表时间：
2004-02-24
影响因子：
11.1
作者：
Malnic, B;Godfrey, PA;Buck, LB
通讯作者：
Buck, LB
影响因子：
29
作者：
Chambers AP;Sorrell JE;Haller A;Roelofs K;Hutch CR;Kim KS;Gutierrez-Aguilar R;Li B;Drucker DJ;D'Alessio DA;Seeley RJ;Sandoval DA
通讯作者：
Sandoval DA