Regulation of glucagon-like peptide-1 synthesis and secretion in the GLUTag enteroendocrine cell line
Regulation of glucagon-like peptide-1 synthesis and secretion in the GLUTag enteroendocrine cell line
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DOI：
10.1210/en.139.10.4108
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发表时间：
1998-10-01
期刊：
影响因子：
4.8
通讯作者：
Drucker, DJ
中科院分区：
文献类型：
--
作者：
Brubaker, PL;Schloos, J;Drucker, DJ
从肠道释放的胰高血糖素样肽-1（GLP-1）是葡萄糖依赖性胰岛素分泌的有效刺激剂。为了阐明调节GLP-1分泌的因素，我们研究了肠内分泌GLUTag细胞系。通过分别用毛喉素或佛波醇12，13-二丁酸酯激活蛋白激酶A或C，GLP-1分泌以剂量依赖性方式被刺激（在100 μ M时分别为2.3 +/-0.5倍，在0.3 μ M时为4.3 +/-0.6倍; P < 0.01-0.001）。在测试的调节肽中，只有葡萄糖依赖性促胰岛素肽刺激GLP-1的释放（在0.1 μ M时为2.3 +/- 0.2倍; P < 0.001）;胰高血糖素没有作用，矛盾的是，抑制性神经肽生长抑素-14轻微增加分泌（在0.01 μ M时为1.6 +/- 0.3倍; P < 0.05）。在几种神经递质的测试中，只有胆碱能激动剂卡巴胆碱和氨甲酰胆碱以剂量依赖性方式刺激肽分泌（在1000 μ M时为2.3 +/- 0.5和1.7 +/- 0.3倍; P < 0.06-0.001）; β-肾上腺素能激动剂异丙肾上腺素和氯通道抑制剂γ-氨基丁酸不影响GLP-1的释放。长链单不饱和脂肪酸（18：1），但不饱和脂肪酸（16：0），也刺激GLP-1的释放（在150 μ M时为1.7 +/-0.1倍; P < 0.001）。与胰高血糖素原基因中cAMP反应元件的存在一致，用毛喉素激活蛋白激酶A依赖性途径使胰高血糖素原信使RNA转录水平增加2倍（P < 0.05）;葡萄糖依赖性促胰岛素肽和佛波醇12，13-二丁酸酯没有影响。因此，通过与使用原代L细胞培养物或体内模型获得的结果进行比较，GLUTag细胞似乎对控制肠道GLP-1分泌的调节机制有适当的反应。
Glucagon-like peptide-1 (GLP-1) released from the intestine is a potent stimulator of glucose-dependent insulin secretion. To elucidate the factors regulating GLP-1 secretion, we have studied the enteroendocrine GLUTag cell line. GLP-1 secretion was stimulated in a dose-dependent fashion by activation of protein kinase A or C with forskolin or phorbol 12,13-dibutyrate, respectively (by 2.3 +/- 0.5-fold at 100 mu M and 4.3 +/- 0.6-fold at 0.3 mu M, respectively; P < 0.01-0.001). Of the regulatory peptides tested, only glucose-dependent insulinotropic peptide stimulated the release of GLP-1 (by 2.3 +/- 0.2-fold at 0.1 mu M; P < 0.001); glucagon was without effect, and paradoxically, the inhibitory neuropeptide somatostatin-14 increased secretion slightly (by 1.6 +/- 0.3-fold at 0.01 mu M; P < 0.05). In tests of several neurotransmitters, only the cholinergic agonists carbachol and bethanechol stimulated peptide secretion in a dose-dependent fashion (by 2.3 +/- 0.5- and 1.7 +/- 0.3-fold at 1000 mu M; P < 0.06-0.001); the beta-adrenergic agonist isoproterenol and the chloride channel inhibitor gamma-aminobutyric acid did not affect release of GLP-1. Long chain monounsaturated fatty acids (18:1), but not saturated fatty acids (16:0), also stimulated the release of GLP-1 (by 1.7 +/- 0.1-fold at 150 mu M; P < 0.001). Consistent with the presence of a cAMP response element in the proglucagon gene, activation of the protein kinase A-dependent pathway with forskolin increased proglucagon messenger RNA transcript levels by 2-fold (P < 0.05); glucose-dependent insulinotropic peptide and phorbol 12,13-dibutyrate were without effect. Therefore, by comparison with results obtained using primary L cell cultures or in vivo models, GLUTag cells appear to respond appropriately to the regulatory mechanisms controlling intestinal GLP-1 secretion.