Role of CCK-A Receptor for Pancreatic Function in Mice: A Study in CCK-A Receptor Knockout Mice
Role of CCK-A Receptor for Pancreatic Function in Mice: A Study in CCK-A Receptor Knockout Mice
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DOI：
10.1097/00006676-200204000-00011
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发表时间：
2002-04
期刊：
影响因子：
2.9
通讯作者：
S. Takiguchi;Shinj Suzuki;Yuko Sato;S. Kanai;K. Miyasaka;A. Jimi;H. Shinozaki;Y. Takata;A. Funakoshi;A. Kono;O. Minowa;Tomoko Kobayashi;T. Noda
中科院分区：
文献类型：
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作者：
S. Takiguchi;Shinj Suzuki;Yuko Sato;S. Kanai;K. Miyasaka;A. Jimi;H. Shinozaki;Y. Takata;A. Funakoshi;A. Kono;O. Minowa;Tomoko Kobayashi;T. Noda
胆囊收缩素（CCK）家族的肽和受体存在于整个大脑和胃肠道。CCK受体在药理学上可分为两种亚型：CCK-A和CCK-B。CCK-A受体在小鼠胰腺中富集。目的研究CCK-A受体缺陷小鼠胚胎干细胞基因打靶突变体的胰腺功能。靶向载体在外显子2中含有lacZ和neo插入。方法采用离体分散腺泡释放淀粉酶的方法检测外分泌功能。在体内研究中，收集胆胰液的混合物，并在给予各种刺激剂后测定淀粉酶、碳酸氢盐和胆汁酸的产量。结扎胆囊的胆囊管和幽门以排除胆囊收缩和胃酸的参与。测定胰腺酶含量，并进行HE和lacZ染色的组织学检查。为了检查内分泌功能，测定口服葡萄糖耐量试验（2 g/kg）。结果3种基因型的体重、胰腺湿重、胰腺酶含量差异无统计学意义。CCK-8对CCK-AR（-/-）小鼠体内和体外的淀粉酶释放以及体内碳酸氢盐分泌没有刺激作用，而对其他刺激物的反应在（-/-）小鼠中很明显。无论基因型如何，促胰液素的施用都不会增加碳酸氢盐的分泌。在（−/−）小鼠中观察到正常的葡萄糖耐量。腺泡细胞、胰岛和导管细胞用lacZ染色，HE染色未发现病理改变。结论CCK-A受体对小鼠胰腺外分泌起重要作用，但对维持葡萄糖浓度和胰腺生长不是必需的。
Introduction The cholecystokinin (CCK) family of peptides and receptors is present throughout the brain and gastrointestinal tract. The CCK receptors can be pharmacologically subdivided into two subtypes: CCK-A and CCK-B. CCK-A receptor is enriched in the pancreas of mice. Aims To determine pancreatic functions in a CCK-A receptor deficient mouse mutant generated by gene targeting in embryonic stem cells. The targeting vector contained lacZ and neo insertions in exon 2. Methodology To examine exocrine functions, amylase release from the dispersed acini in vitro was examined. In the in vivo study, the mixture of bile–pancreatic juice was collected, and amylase, bicarbonate, and bile acid outputs were determined after the administration of various stimulants. The cystic duct of the gallbladder and the pylorus were ligated to exclude the involvement of gallbladder contraction and gastric acid. Pancreatic enzyme content was measured, and histologic examinations by HE and lacZ staining were conducted. To examine endocrine functions, oral glucose tolerance test (2 g/kg) was determined. Results The body weight, pancreatic wet weight, and enzyme content in the pancreas were similar among the three genotypes. Amylase release in vivo and in vitro and bicarbonate secretion in vivo were not stimulated by CCK-8 in CCK-AR (−/−) mice, whereas the responses to other stimulants were substantial in (−/−) mice. Administration of secretin did not increase bicarbonate secretion regardless of genotype. A normal glucose tolerance was observed in (−/−) mice. Acinar cells, islets, and duct cells were stained by lacZ, and HE staining revealed no pathologic findings. Conclusion The CCK-A receptor is important for pancreatic exocrine secretion, but not essential for maintaining glucose concentration and pancreatic growth in mice.