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胰高血糖素样肽-1(GLP-1):一种在糖尿病治疗中具有潜在价值的肠道激素。

Glucagon-like peptide-1 (GLP-1): a gut hormone of potential interest in the treatment of diabetes.

作者信息

Ahrén B

机构信息

Department of Medicine, Lund University, Malmö, Sweden.

出版信息

Bioessays. 1998 Aug;20(8):642-51. doi: 10.1002/(SICI)1521-1878(199808)20:8<642::AID-BIES7>3.0.CO;2-K.

Abstract

GLP-1 (glucagon-like peptide-1) is a gut hormone which is released into the blood stream after feeding. Its main action is to stimulate insulin secretion through potentiating the insulinotropic action of glucose. The peptide is encoded in the glucagon gene and expressed mainly in the gut L cells. It exerts its actions through activating specific receptors of the seven transmembraneous domain-G-protein-coupled type with 463 amino acids. Its main signalling mechanism is activation of adenylate cyclase and formation of cyclic AMP. The peptide also increases the cytoplasmic concentration of Ca2 which is thought to be executed both through a Na(+)-dependent uptake of extracellular Ca2+ and through release of Ca2+ from intracellular Ca2+ stores. GLP-1 also inhibits glucagon secretion and inhibits gastric emptying and gastric acid and pancreatic exocrine secretion. Its integrated action on carbohydrate metabolism results in reduction of circulating glucose, and GLP-1 has therefore been suggested as a therapeutic alternative in diabetes. Finally, GLP-1 is also expressed in neurons in the hypothalamus, and may be involved in the regulation of feeding behaviour, since it inhibits food intake.

摘要

胰高血糖素样肽-1(GLP-1)是一种肠道激素,进食后会释放到血液中。其主要作用是通过增强葡萄糖的促胰岛素作用来刺激胰岛素分泌。该肽由胰高血糖素基因编码,主要在肠道L细胞中表达。它通过激活具有463个氨基酸的七跨膜结构域-G蛋白偶联型特异性受体发挥作用。其主要信号传导机制是激活腺苷酸环化酶并形成环磷酸腺苷。该肽还会增加细胞质中Ca2+的浓度,这被认为是通过细胞外Ca2+的Na(+)-依赖性摄取以及细胞内Ca2+储存释放Ca2+来实现的。GLP-1还抑制胰高血糖素分泌,抑制胃排空、胃酸分泌和胰腺外分泌。它对碳水化合物代谢的综合作用导致循环葡萄糖减少,因此GLP-1被认为是糖尿病治疗的一种替代方法。最后,GLP-1在下丘脑的神经元中也有表达,并且可能参与进食行为的调节,因为它会抑制食物摄入。

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