SECRETION AND ACTION OF PRO-SOMATOSTATIN RELATED PEPTIDE

促生长素抑制素相关肽的分泌和作用

• 批准号: 3232728
• 负责人: JOHN W ENSINCK
• 金额: $ 13.32万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-09-01 至 1989-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3232728
• 关键词: affinity chromatography; antibody neutralization test; antiserum; carbohydrate metabolism; cysteamine; gastrointestinal absorption /transport; gastrointestinal function; gel filtration chromatography; high performance liquid chromatography; homeostasis; hormone regulation /control mechanism; human tissue; hypoglycemia; hypothalamus; immunochemistry; insulin; intestinal mucosa; liver metabolism; monoclonal antibody; nutrition related tag; obesity; organ culture; pancreatic islet function; peptide hormone biosynthesis; peptide hormone metabolism; radioimmunoassay; secretion; somatostatin; synthetic peptide; tissue /cell culture

Somatostatin (SS) is one of several peptides cleaved during the post translational processing of pro-SS. SS and SS-related peptides (SRP) are released by cells in brain, hypothalamus, pancreas and intestine and at least two SRP are known to suppress the secretion of several peptides involved in fuel homeostasis. The overall aim of this proposal is to evaluate the hypothesis that SS28, a product of processing of pro-SS, is preferentially released from the small intestine and, transported to the endocrine pancreas in the circulation, acts as a physiological modulator of postprandial insulin secretion. Four specific questions include: 1) is the small intestine the principal source of circulating SRP?; 2) if so, what are the signals that lead to their secretion?; 3) does SS28 and other precursors exert effects both locally and on distant cells?; and 4) is the secretion of SRP perturbed in and contribute to hormonal changes in pathologic states? These questions will be tested in man, baboon and rat. Measurements of SRP will be made by radioimmunoassay using antisera specific for different regions of pro-SS. These include SS28, SS28(1-12), SS28(1-14), and SS28(15-28), as well as two precursors of SS28 of estimated MW of 12 and 5 K daltons. SRP in the peripheral circulation of normal man will be evaluated in response to oral and IV nutriments, substrates, neurotransmitters, and peptides. The content of SRP and their biosynthetic pathways will be examined in human intestinal mucosa obtained by biopsy. Possible alterations in secretion of SRP in man with metabolic and intestinal disorders will be evaluated. Hepatic clearance of SRP will be examined in the baboon. The release of SRP into the venous and luminal effluent in the in situ perfused rat small intestine will be evaluated to determine if different peptides are secreted. To test the hypothesis that circulating SS28 and possibly other SRP influence insulin secretion, passive neutralization experiments with antisera against SRP, and depletion of tissue levels of SRP with cysteamine will be carried out. The long-term objective is to determine if SRP release during nutriment absorption act to restrain postprandial events in fuel homeostasis.

生长抑素（SS）是在邮政期间切割的几种肽之一 Pro-Ss的翻译处理。 SS和SS相关肽（SRP）为 由细胞在大脑，下丘脑，胰腺和肠中释放，在 已知至少有两个SRP抑制了几种肽的分泌 参与燃料稳态。 该提议的总体目的是 评估以下假设：SS28是Pro-SS处理的产物，IS 优先从小肠释放，然后运输到 循环中的内分泌胰腺充当 餐后胰岛素分泌。 四个具体问题包括：1）是 小肠是循环SRP的主要来源？ 2）如果是这样， 导致他们分泌的信号是什么？ 3）做SS28和其他 前体对局部和远处的细胞发挥影响？ 4）是 SRP的分泌受干扰并导致激素变化 病态状态？ 这些问题将在人，狒狒和老鼠中进行测试。 SRP的测量将通过放射免疫测定法使用Antisera进行 专门针对Pro-Ss的区域。 其中包括SS28，SS28（1-12）， SS28（1-14）和SS28（15-28），以及SS28的两个前体 MW为12和5 K daltons。 正常人的周围循环中的SRP 将根据口服和静脉营养，基材，响应评估 神经递质和肽。 SRP及其生物合成的内容 将在活检获得的人肠粘膜中检查途径。 在具有代谢和代谢和 将评估肠道疾病。 SRP的肝间隙将 在狒狒中检查。 SRP释放到静脉和腔内 原位灌注大鼠小肠中的废水将被评估为 确定是否分泌不同的肽。 检验以下假设 循环SS28以及其他SRP可能影响胰岛素分泌， 用反塞拉针对SRP进行的被动中和实验，耗尽 将执行与cysteamine的SRP的组织水平。 长期 目的是确定营养吸收期间的SRP是否释放到 在燃料稳态中限制餐后事件。