Regulation of amylin release from cultured rabbit gastric fundic mucosal cells.
Regulation of amylin release from cultured rabbit gastric fundic mucosal cells.
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DOI：
10.1186/1472-6793-3-13
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发表时间：
2003-10-22
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影响因子：
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通讯作者：
Calam, John
中科院分区：
文献类型：
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作者：
Beales, Ian L P;Calam, John
背景技术背景：胰淀素（胰岛淀粉样多肽）是一种激素，具有调节葡萄糖稳态、胃运动和分泌功能以及胃保护作用。在胃粘膜中，发现胰淀素与生长抑素共定位于D细胞中。调节胃胰淀素释放的因素尚不清楚。在这项研究中，我们研究了在原代培养的胃粘膜细胞胰淀素释放的调节。将通过逆流淘析富集D细胞的兔胃底粘膜细胞培养40小时。胰淀素和生长抑素释放超过2小时，在响应激动剂assessed.Results：胰淀素释放显着增强蛋白激酶C与佛波醇-12-肉豆蔻酸-13-乙酸酯，腺苷酸环化酶与毛喉素和升高细胞内钙与A23187的激活。胆囊收缩素（CCK）、肾上腺素和胰高血糖素样肽-1（GLP-1）均以剂量依赖性方式刺激胰淀素释放。CCK刺激的最大释放大于肾上腺素或GLP-1，即使后两者的作用被异丁基甲基黄嘌呤增强。卡巴胆碱（51-59%）和奥曲肽（33-42%）显著抑制刺激的胰淀素释放。结论：培养的D细胞模型提供了一种研究胰淀素释放的方法。胰淀素分泌受Ca 2 +/蛋白激酶C和腺苷酸环化酶途径的受体依赖性和非依赖性激活的刺激。抑制涉及毒蕈碱受体的激活和生长抑素的自动调节。
BACKGROUND: Amylin (islet amyloid polypeptide) is a hormone with suggested roles in the regulation of glucose homeostasis, gastric motor and secretory function and gastroprotection. In the gastric mucosa amylin is found co-localised with somatostatin in D-cells. The factors regulating gastric amylin release are unknown. In this study we have investigated the regulation of amylin release from gastric mucosal cells in primary culture. Rabbit fundic mucosal cells enriched for D-cells by counterflow elutriation were cultured for 40 hours. Amylin and somatostatin release over 2 hours in response to agonists were assessed.RESULTS: Amylin release was significantly enhanced by activation of protein kinase C with phorbol-12-myristate-13-acetate, adenylate cyclase with forskolin and elevation of intracellular calcium with A23187. Cholecystokinin (CCK), epinephrine and glucagon-like peptide-1 (GLP-1) each stimulated amylin release in a dose-dependent manner. Maximal CCK-stimulated release was greater than either epinephrine or GLP-1, even when the effects of the latter two were enhanced by isobutylmethylxanthine. Stimulated amylin release was significantly inhibited by carbachol (by 51-59%) and octreotide (by 33-42%). Somatostatin release paralleled that of amylin.CONCLUSIONS: The cultured D-cell model provides a means of studying amylin release. Amylin secretion is stimulated by receptor-dependent and -independent activation of Ca2+/protein kinase C and adenylate cyclase pathways. Inhibition involves activation of muscarinic receptors and auto-regulation by somatostatin.