LUMINAL GLUCAGON-LIKE PEPTIDE-1(7-36) AMIDE-RELEASING FACTORS IN THE ISOLATED VASCULARLY PERFUSED RAT COLON

LUMINAL GLUCAGON-LIKE PEPTIDE-1(7-36) AMIDE-RELEASING FACTORS IN THE ISOLATED VASCULARLY PERFUSED RAT COLON
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DOI:
10.1677/joe.0.1450521
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发表时间:
1995-06-01
影响因子:
4
通讯作者:
CUBER, JC
CUBER, JC
中科院分区:
医学2区
文献类型:
--
作者:
PLAISANCIE, P;DUMOULIN, V;CUBER, JC

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胰高血糖素样肽-1(GLP-1)在进食后从肠道远端的内分泌细胞释放。GLP-1分泌部分受激素和/或神经机制控制。然而,结肠L细胞的刺激也可以直接由管腔内容物发生。在本研究中,使用离体血管灌注的大鼠结肠检查了这一点。GLP-1免疫反应性在管腔输注后的门静脉流出物中测量。结肠内容物中发现的多种化合物(营养素、纤维、胆汁酸、短链脂肪酸(SCFA))。油酸(100 mM)或氨基酸混合物(总浓度250 mM)或淀粉(0.5%,w/v)未使GLP-1分泌增加超过基础值。药理学浓度的葡萄糖(250 mM)引起GLP-1的显著释放,在输注结束时达到最大值(基础值的400%),而5 mM葡萄糖对分泌无影响。果胶在0.1-0.5%(w/v)范围内诱发GLP-1的剂量依赖性释放,当输注0.5%果胶时,最大反应为基础值的360%。纤维素或阿拉伯树胶(0.5%)没有改变GLP-1分泌。SCFA乙酸盐、丙酸盐或丁酸盐(5、20和100 mM)未诱导GLP-1的显著释放。在检测的四种胆汁酸(即牛磺胆酸盐、胆酸盐、脱氧胆酸盐和猪脱氧胆酸盐)中,最后一种在引发GLP-1应答方面最有效,当分别给予2和20 mM胆汁酸时,最大释放为基础值的300%和400%。总之,一些纤维和胆汁酸能够释放大鼠结肠GLP-1,并可能有助于结肠L细胞的分泌活性。
Glucagon-like peptide-1 (GLP-1) is released from endocrine cells of the distal part of the gut after ingestion of a meal. GLP-1 secretion is, in part, under the control of hormonal and/or neural mechanisms. However, stimulation of the colonic L cells may also occur directly by the luminal contents. This was examined in the present study, using an isolated vascularly perfused rat colon. GLP-1 immunoreactivity was measured in the portal effluent after luminal infusion. of a variety of compounds which are found in colonic contents (nutrients, fibers, bile acids, short-chain fatty acids (SCFAs)). Oleic acid (100 mM) or a mixture of amino acids (total concentration 250 mM), or starch (0.5%, w/v) did not increase GLP-1 secretion over basal value. A pharmacological concentration of glucose (250 mM) elicited a marked release of GLP-1 which was maximal at the end of infusion (400% of basal), while 5 mM glucose was without effect on secretion. Pectin evoked a dose-dependent release of GLP-1 over the range 0.1-0.5% (w/v) with a maximal response at 360% of basal when 0.5% pectin was infused. Cellulose or gum arabic (0.5%) did not modify GLP-1 secretion. The SCFAs acetate, propionate or butyrate (5, 20 and 100 mM) did not induce a significant release of GLP-1. Among the four bile acids tested, namely taurocholate, cholate, deoxycholate and hyodeoxycholate, the last one was the most potent at eliciting a GLP-1 response with a maximal release at 300% and 400% of the basal value when 2 and 20 mM bile acid were administered respectively. In conclusion, some fibres and bile acids are capable of releasing colonic GLP-1 in rats and may contribute to the secretory activity of colonic L cells.