PRO-SOMATOSTATIN RELATED PEPTIDES

生长抑素原相关肽

• 批准号: 3232731
• 负责人: JOHN W ENSINCK
• 金额: $ 22.5万
• 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 1992-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3232731
• 关键词: Cercopithecidae; antibody neutralization test; antiserum; bioperiodicity; cholecystokinin; disease /disorder model; drug related diabetes mellitus; enzyme linked immunosorbent assay; gastric inhibitory peptide; gastrointestinal nutrient absorption; glucagon; glucose metabolism; homeostasis; hormone regulation /control mechanism; human subject; human tissue; insulin; laboratory mouse; laboratory rabbit; laboratory rat; monoclonal antibody; noninsulin dependent diabetes mellitus; nutrition related tag; pancreatic islet function; peptide hormone analog; peptide hormone biosynthesis; peptide hormone metabolism; radioimmunoassay; secretin; secretion; somatostatin; streptozotocin

The overall hypothesis is that insulinotropic peptides from the and somatostatin-28 [S-28], a "decretin", act in concert to modulate insulin secretion on during absorption and assimilation of nutrients. Specific questions include: 1) Do "ineretine" and S-28 differentially alter the periodicity and threshold of glucose-mediated insulin secretion in vitro and in vivo? 2) Do S-28 and "incretins" module periodicity and kinetice of insulin secretion during nutrient absorption and is there a hierarchal order of importance amongst the putative "ineretins"? 3) Do elevated levels of S-28, contribute to defective insulin secretion in diabetes sellitue? The hypothesis is based on emerging information that enteric peptides including secretion, CCK, GIP and GLP-1 (7-36) potentiate the release of insulin, whereas, S-28 also from the gut, way inhibit insulin secretion. From pancreatic islet models, insulin appears to be released at varying glucose threabolds and it is plausible that "incretins" and S-28 may shift the threshold and rate of insulin release by glucose and also alter the periodicity and/or amplitude of its cyclic release. Since glucone-mediated first-phase insulin secretion [equated with threshold sensitivity] is deficient in Type II diabetes mellitus, it is possible that S-28 may adversely shift the sensitivity threshold in this disorder. To address these questions, we will evaluate the effects of secretion, CCK, GIP and GLP-1 (7-36) and S-28, separately and together, on the threshold and rate of insulin release in the perfused rat pancreas and in man. Periodicity and amplitude of insulin release will also be used. To evaluate the "physiologic" role of "incretine" and S-28 in modulating insulin secretion in vivo, baboons will be studied before and after immunoneutralization of circulating "incretins" and S-28, separately and together, during nutrient intake. To evaluate the role of S-28 on insulin secretion in defective B-cells, baboons, treated with small doses of streptozocin to induce early changes in insulin secretion, and the Goto rat model of Type II diabetes mellitus vill be examined. Insulin secretion before and after immunoneutralization with S-28 monoclonal antibodies during nutrient absorption will be tested. The results of these experiments should provide a more comprehensive view of the physiologic importance of the entero-insular axis in modulating insulin secretion.

总体假设是来自和 Somatostatin-28 [S-28]，一个“律师”，共同调节胰岛素 养分吸收和吸收期间的分泌。具体的 问题包括：1）做“ ineretine”和s-28差异改变 葡萄糖介导的胰岛素分泌的周期性和阈值体外 和体内？ 2）DO S-28和“肠肠毒素”模块周期性和动力学 营养吸收过程中胰岛素分泌的 假定的“ ineretins”之间的层次阶层？ 3）做 S-28的水平升高，导致胰岛素分泌有缺陷 糖尿病卖出？该假设基于新兴信息 包括分泌，CCK，GIP和GLP-1在内的肠肽（7-36） 增强胰岛素的释放，而S-28也从肠道中释放 抑制胰岛素分泌。从胰岛模型中，胰岛素出现 要在不同的葡萄糖恐怖分子上释放，这是合理的 “肠魔”和S-28可能会改变胰岛素释放的阈值和速率 通过葡萄糖，也改变其周期性的周期性和/或振幅 发布。由于葡萄酮介导的第一相胰岛素分泌[等同 具有阈值灵敏度]缺乏II型糖尿病， S-28可能会不利地转移灵敏度阈值 在这个疾病中。为了解决这些问题，我们将评估 分泌的效果，CCK，GIP和GLP-1（7-36）和S-28，分别 一起，在灌注中胰岛素释放的阈值和速率 老鼠胰腺和人。胰岛素释放的周期性和振幅 也将使用。评估“惯性”和 S-28在调节体内胰岛素分泌时，将研究狒狒 在循环“肠t”和之后进行免疫和之后 在养分摄入过程中，S-28分别和一起。评估 S-28在有缺陷的B细胞，狒狒中的胰岛素分泌的作用 用少量链链球菌素诱导胰岛素的早期变化 分泌，以及II型糖尿病的Goto大鼠模型Mellitus Vill 检查。免疫和之后的胰岛素分泌 将测试营养吸收过程中的S-28单克隆抗体。 这些实验的结果应提供更全面的 肠道轴轴的生理重要性的视图 调节胰岛素分泌。