Glucagon-like peptide-1-(7-36)amide is transformed to glucagon-like peptide-1-(9-36)amide by dipeptidyl peptidase IV in the capillaries supplying the L cells of the porcine intestine
Glucagon-like peptide-1-(7-36)amide is transformed to glucagon-like peptide-1-(9-36)amide by dipeptidyl peptidase IV in the capillaries supplying the L cells of the porcine intestine
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DOI：
10.1210/en.140.11.5356
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发表时间：
1999-11-01
期刊：
影响因子：
4.8
通讯作者：
Holst, JJ
中科院分区：
文献类型：
--
作者：
Hansen, L;Deacon, CF;Holst, JJ
促胰岛素激素胰高血糖素样肽-1（GLP-1）以活性形式GLP-1-（7-36）酰胺储存在肠L细胞中，但超过一半的内源性肽以无活性的N-末端截短形式GLP-1-（9-36）酰胺循环。本研究在体外检测了从猪回肠新分泌的GLP-1（分离的灌注制剂）和体内尽管从猪回肠提取的GLP-1主要是完整的肽，（94.6 +/- 1.7%），分泌的大部分GLP-1已经在体外和体外降解为截短形式（53.8 +/-：0.9%完整）和体内（32.9 +/- 10.8%完整）。在存在特异性二肽基肽酶TV（DPP TV）抑制剂（缬氨酸-吡咯烷）的情况下，在基础（99%完整; P < 0.05）和刺激（86-101%完整; P < 0.05）条件下，从灌注回肠释放的完整GLP-1比例增加。免疫组织化学和组织化学研究显示，特定的DPP电视染色刷状缘上皮细胞以及毛细血管内皮细胞。双重染色显示DPP IV阳性毛细血管和含GLP-1的L细胞并置。根据这些结果，我们认为GLP-1在进入含有DPP IV的肠粘膜引流血管时发生降解。
The insulinotropic hormone glucagon-like peptide-1 (GLP-1) is stored in the intestinal L cell in an active form, GLP-1-(7-36)amide, but more than half of the endogenous peptide circulates in an inactive, N-terminally truncated form, GLP-1-(9-36)amide. This study examined the GLP-1 newly secreted from the porcine ileum, in vitro (isolated perfused preparation) and in vivo (anesthetized pig), to determine where this conversion occurs.Although the GLP-1 extractable from the porcine ileum is predominantly the intact peptide (94.6 +/- 1.7%), a large proportion of the GLP-1 that is secreted has already been degraded to the truncated form both in, vitro (53.8 +/-: 0.9% intact) and in, vivo (32.9 +/- 10.8% intact). In the presence of a specific dipeptidyl peptidase TV (DPP TV) inhibitor (valine-pyrrolidide), the proportion of intact GLP-1 released from the perfused ileum was increased under both basal(99% intact; P < 0.05) and stimulated (86-101% intact; P < 0.05) conditions. Immunohistochemical and histochemical studies revealed specific DPP TV staining in the brush border epithelium as well as in the capillary endothelium. Double staining showed juxtapositioning of DPP IV-positive capillaries and GLP-1-containing L cells. From these results, we suggest that GLP-1 is degraded as it enters the DPP IV containing blood vessels draining the intestinal mucosa.