NEUROENDOCRINE REGULATION OF PANCREATIC HORMONE SECRETION

胰腺激素分泌的神经内分泌调节

• 批准号: 6907125
• 负责人: GEORGE H GREELEY
• 金额: $ 19.44万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6907125
• 关键词: biological signal transduction; cholecystokinin; elastases; enzyme activity; gastrin releasing peptide; gastrointestinal hormones; gastrointestinal surgery; hormone regulation /control mechanism; immunocytochemistry; laboratory rat; neuroendocrine system; pancreas; protein structure function; radioimmunoassay; secretion; somatostatin

Mechanisms underlying nutrient induced intestinal cholecystokinin (CCK) secretion are not completely described. Research from several laboratories show that intestinal CCK secretion is stimulated by luminal CCK releasing factors. Apelin is the newest member of a family of peptides shown to signal intestinal CCK secretion by an action from within the intestinal lumen. Apelin is unique in that gastric apelin is produced in stomach exocrine and endocrine cells implying that apelin acts by endocrine as well as luminal routes to cause CCK secretion. Another unique feature is that apelin is secreted into the stomach lumen rather than the small intestinal lumen. This proposal examines the hypothesis that gastric apelin plays a role as a physiological regulator of intestinal CCK secretion. To test this hypothesis studies are proposed to define the importance of luminal and systemic apelin in the physiological regulation of CCK secretion using surgically prepared stomach and intestinal perfusion rat models. Our Specific Aims are: Aim 1. To test the hypothesis that dietary nutrients activate secretion of gastric apelin. Aim 2. To test the hypothesis that gastric apelin plays a role in the regulation of intestinal cholecystokinin (CCK) secretion. Preliminary data show abundant apelin-positive cells in the stomach epithelium, that the gut lumen and systemic circulation contain apelin, that apelin stimulates CCK secretion in vitro and in vivo in the rat, and that luminal immunoneutralization of apelin decreases nutrient-induced CCK secretion. In Aim 1 we expect to show that gastric apelin is produced in at least two different gastric cell types, to define nutrient-induced apelin secretion into plasma and luminal compartments, and show that ligands which activate parietal cell secretion simultaneously cause apelin release into the gastric lumen. In Aim 2 we will define the importance of gastric apelin in nutrient-induced CCK secretion using immunoneutralization. It is important to understand mechanisms that signal CCK secretion in view of the roles CCK may play in various digestive diseases and appetite disorders. A better appreciation of regulation of CCK secretion will help in understanding the pathophysiology of these disease processes and give insight into new clinical therapies.

营养诱导的肠内胆囊收缩素（CCK）分泌机制尚不完全清楚。几个实验室的研究表明，肠道CCK分泌是由腔内CCK释放因子刺激的。Apelin是一个多肽家族的最新成员，该家族显示通过肠腔内的作用来指示肠道CCK分泌。Apelin的独特之处在于胃Apelin是在胃的外分泌和内分泌细胞中产生的，这意味着Apelin通过内分泌和腔内途径引起CCK的分泌。另一个独特的特点是apelin分泌到胃腔而不是小肠腔。本研究提出胃尖蛋白作为肠道CCK分泌的生理调节因子的假说。为了验证这一假设，我们提出利用手术制备的大鼠胃和肠灌注模型来确定腔内和全身apelin在CCK分泌的生理调节中的重要性。我们的具体目标是：验证膳食营养物质激活胃胃上皮细胞分泌的假说。目标2。验证胃apelin参与肠内胆囊收缩素（CCK）分泌调节的假说。初步数据显示胃上皮中有大量的apelin阳性细胞，肠腔和体循环中含有apelin， apelin在体外和体内刺激CCK的分泌，并且apelin的腔内免疫中和减少了营养诱导的CCK分泌。在Aim 1中，我们期望表明胃apelin是在至少