Gut-expressed gustducin and taste receptors regulate secretion of glucagon-like peptide-1
Gut-expressed gustducin and taste receptors regulate secretion of glucagon-like peptide-1
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DOI：
10.1073/pnas.0706890104
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发表时间：
2007-09-18
影响因子：
11.1
通讯作者：
Egan, Josephine M.
中科院分区：
文献类型：
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作者：
Jang, Hyeung-Jin;Kokrashvili, Zaza;Egan, Josephine M.
胰高血糖素样肽-1(GLP-1)是由肠道内分泌的L细胞对葡萄糖的反应而释放出来的，调节食欲、胰岛素分泌和肠道运动。目前尚不清楚口服葡萄糖是如何诱导GLIP-1分泌的。我们发现人十二指肠L细胞表达甜味受体、味觉G蛋白Gustducin和其他几种味觉转导元件。小鼠肠道L细胞也表达a-gustducin。α-Gustducin基因缺失的小鼠摄入葡萄糖后，GLP-1的分泌以及血浆胰岛素和血糖的调节都出现了缺陷。从α-Gustducin缺失的小鼠分离的小肠和肠道绒毛对葡萄糖的反应显示明显的GILP-1分泌缺陷。人L细胞株NCI-H716表达α-Gustducin、味觉受体和其他几个味觉信号元件。糖和非热量甜味剂三氯蔗糖可促进NCI-H716细胞释放GLP-1，甜味受体拮抗剂乳糖醇或α-Gustducin的siRNA可阻断GLP-1的释放。我们得出结论，肠道的L细胞通过与舌头味觉细胞相同的机制来“品尝”葡萄糖。调节肠道“味觉细胞”中GLP-1的分泌可能为肥胖、糖尿病和肠道运动异常提供重要的治疗方法。
Glucagon-like peptide-1 (GLP-1), released from gut endocrine L cells in response to glucose, regulates appetite, insulin secretion, and gut motility. How glucose given orally, but not systemically, induces GILP-1 secretion is unknown. We show that human duodenal L cells express sweet taste receptors, the taste G protein gustducin, and several other taste transduction elements. Mouse intestinal L cells also express a-gustducin. Ingestion of glucose by alpha-gustducin null mice revealed deficiencies in secretion of GLP-1 and the regulation of plasma insulin and glucose. Isolated small bowel and intestinal villi from alpha-gustducin null mice showed markedly defective GILP-1 secretion in response to glucose. The human L cell line NCI-H716 expresses a-gustducin, taste receptors, and several other taste signaling elements. GLP-1 release from NCI-H716 cells was promoted by sugars and the noncaloric sweetener sucralose, and blocked by the sweet receptor antagonist lactisole or siRNA for a-gustducin. We conclude that L cells of the gut "taste" glucose through the same mechanisms used by taste cells of the tongue. Modulating GLP-1 secretion in gut "taste cells" may provide an important treatment for obesity, diabetes and abnormal gut motility.