What do we know about the secretion and degradation of incretin hormones?
What do we know about the secretion and degradation of incretin hormones?
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DOI：
10.1016/j.regpep.2004.06.007
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发表时间：
2005-06-15
影响因子：
--
通讯作者：
Deacon, CF
中科院分区：
文献类型：
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作者：
Deacon, CF
肠促胰岛素激素、葡萄糖依赖性胰岛素促肽（GIP）和胰高血糖素样肽-1 （GLP-1）由位于肠粘膜的内分泌细胞分泌，可增强食物诱导的胰岛素分泌。食物摄入后血浆中GIP和GLP-1浓度迅速上升，肠道内未吸收的营养物质的存在是其分泌的强烈刺激。营养物质可以通过直接接触k细胞（GIP）和l细胞（GLP-1）来刺激这两种激素的释放，这可能是最重要的信号。然而，营养物质也通过其他机制间接刺激GLP-1和GIP的分泌。肠促胰岛素激素的分泌可通过神经调节，胆碱能毒蕈碱、β -肾上腺素能和肽能（胃泌素释放肽，GRP）纤维通常具有积极作用，而α -肾上腺素能和生长抑素能纤维则抑制其分泌。激素因素也可能影响促肠促胰岛素的分泌。生长抑素通过旁分泌机制对K细胞和l细胞的活性产生局部抑制作用，而至少在啮齿类动物中，来自近端肠的GIP对GLP-1的分泌有刺激作用，可能是通过涉及GRR的神经回路介导的。一旦它们被释放，GLP-1和GIP都会迅速降解。普遍存在的酶，二肽基肽酶IV （DPP IV）切割n端，去除二肽，从而使两肽失活，因为n端对受体结合至关重要。随后，肽可以被其他酶降解并以特定器官的方式提取。完整的肽在通过肝床的过程中失活，并进一步被外周组织代谢，而肾脏对代谢物的最终消除很重要。(c) 2004 Elsevier B.V.版权所有
The incretin hormones, glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1) are secreted from endocrine cells located in the intestinal mucosa, and act to enhance meal-induced insulin secretion. GIP and GLP-1 concentrations in the plasma rise rapidly after food ingestion, and the presence of unabsorbed nutrients in the intestinal lumen is a strong stimulus for their secretion. Nutrients can stimulate release of both hormones by direct contact with the K-cell (GIP) and L-cell (GLP-1), and this may be the most important signal. However, nutrients also stimulate GLP-1 and GIP secretion indirectly via other mechanisms. Incretin hormone secretion can be modulated neurally, with cholinergic muscarinic, beta-adrenergic and peptidergic (gastrin-releasing peptide, GRP) fibres generally having positive effects, while secretion is restrained by alpha-adrenergic and somatostatinergic fibres. Hormonal factors may also influence incretin hormone secretion. Somatostatin exerts a local inhibitory effect on the activity of both K- and L-cells via a paracrine mechanism, while, in rodents at least, GIP from the proximal intestine has a stimulatory effect on GLP-1 secretion, possibly mediated via a neural loop involving GRR Once they have been released, both GLP-1 and GIP are subject to rapid degradation. The ubiquitous enzyme, dipeptidyl peptidase IV (DPP IV) cleaves N-terminally, removing a dipeptide and thereby inactivating both peptides, because the N-terminus is crucial for receptor binding. Subsequently, the peptides may be degraded by other enzymes and extracted in an organ-specific manner. The intact peptides are inactivated during passage across the hepatic bed and further metabolised by the peripheral tissues, while the kidney is important for the final elimination of the metabolites. (c) 2004 Elsevier B.V. All rights reserved.