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Regulation of Stomach Ghrelin

胃饥饿素的调节

基本信息

批准号：
7808508
负责人：
GEORGE H GREELEY
金额：
$ 26.55万
依托单位：
UNIVERSITY OF TEXAS MED BR GALVESTON
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-07-01 至 2010-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7808508
关键词：
Body Weight Body Weight decreased Burn injury Capsaicin Cells Cholecystokinin Clinical Coupling Data Development Dietary intake Disease Eating Endocrine Endocrine system Epithelium Feedback Fiber Genes Glucagon Goals Growth Homeostasis Hormonal Hormones Human Hypothalamic structure Insulin-Like Growth Factor I Intake Link Malignant Neoplasms Metabolism Molecular Morbidity - disease rate Neurosecretory Systems Nutrient Nutritional Nutritional status Pancreas Pancreatic Hormones Patients Physiological Pituitary Gland Play Process Production Rattus Regulation Regulatory Element Research Role Signal Transduction Somatotropin Stomach Testing Tissues Trauma Treatment-Related Cancer Wasting Syndrome Weight Gain Work base energy balance gastrointestinal gastrointestinal system ghrelin human ghrelin innovation insight mortality novel novel therapeutics promoter treatment strategy

项目摘要

DESCRIPTION (provided by applicant): Our long-term working hypothesis is that the recently discovered stomach hormone, ghrelin, is a critical signal of nutritional status to the growth hormone (GH) neuroendocrine axis serving to integrate energy balance and the growth process. The primary goal of this research is to define physiological and molecular mechanisms underlying the regulation of stomach ghrelin production, secretion and action. Preliminary Findings demonstrate that stomach ghrelin expression and secretion are regulated by dietary and gastrointestinal and pancreatic hormonal manipulations, and that there is a stomach ghrelin-pituitary GH axis. Our Specific Aims are: Aim 1. To test the hypotheses that stomach ghrelin plays a role in the regulation of pituitary GH secretion; that a bi-directional feedback loop exists 3etween pituitary GH and stomach ghrelin secretion; that the stimulatory action of ghrelin on GH secretion is modulated by dietary intake; and that vagal capsaicin sensitive fibers participate in ghrelin secretion and ghrelin-activated GH secretion. Aim 2. To test the hypothesis that stomach ghrelin homeostasis is regulated by cholecystokinin (CCK), glucagon and insulin-like growth factor-1 (IGF-I). Aim 3. To characterize the regulatory elements of the rat and human ghrelin genes and to test the hypotheses that regulatory elements are responsive to GH, glucagon and nutrients. Based upon Preliminary Findings we expect to demonstrate that endogenous stomach ghrelin participates in the regulation of GH secretion, that GH exerts a feedback action on stomach ghrelin secretion and that this ghrelin-GH axis is modulated by dietary intake; that ghrelin homeostasis is regulated by CCK, glucagon and IGF-I; and, that the promoter activity (ie, ghrelin production) of the ghrelin gene is regulated by GH, glucagon and nutrients. Nutritional status is critical in predicting survival in a variety of catabolic diseases and Lrauma. This research is significant because our studies will elucidate physiological and molecular mechanisms behind regulation of GH secretion by ghrelin and will open up new therapeutic strategies for treatment of diseases in which weight loss or gain plays a critical role. This is a compelling reason to define nutritional regulation of ghrelin production and secretion and its role in regulation of GH secretion.

描述（由申请人提供）：我们的长期工作假设是，最近发现的胃激素生长素释放肽是生长激素 (GH) 神经内分泌轴营养状况的关键信号，有助于整合能量平衡和生长过程。本研究的主要目标是确定胃饥饿素产生、分泌和作用调节的生理和分子机制。初步研究结果表明，胃生长素释放肽的表达和分泌受饮食、胃肠道和胰腺激素控制的调节，并且存在胃生长素释放肽-垂体 GH 轴。我们的具体目标是：目标 1. 检验胃 ghrelin 在调节垂体 GH 分泌中发挥作用的假设；垂体 GH 和胃 ghrelin 分泌之间存在双向反馈回路；生长素释放肽对 GH 分泌的刺激作用受饮食摄入量的调节；迷走神经辣椒素敏感纤维参与生长素释放肽分泌和生长素释放肽激活的生长激素分泌。目标 2. 检验胃生长素释放肽稳态受胆囊收缩素 (CCK)、胰高血糖素和胰岛素样生长因子-1 (IGF-I) 调节的假设。目标 3. 表征大鼠和人类生长素释放肽基因的调节元件，并测试调节元件对 GH、胰高血糖素和营养素有反应的假设。根据初步研究结果，我们希望证明内源性胃部生长素释放肽参与 GH 分泌的调节，GH 对胃部生长素释放肽分泌发挥反馈作用，并且该生长素释放肽-GH 轴受到饮食摄入的调节；生长素释放肽稳态受 CCK、胰高血糖素和 IGF-I 调节；并且，生长素释放肽基因的启动子活性（即生长素释放肽产生）受GH、胰高血糖素和营养素调节。营养状况对于预测各种分解代谢疾病和劳马病的生存至关重要。这项研究意义重大，因为我们的研究将阐明生长素释放肽调节 GH 分泌背后的生理和分子机制，并将为治疗体重减轻或增加起关键作用的疾病开辟新的治疗策略。这是定义生长素释放肽产生和分泌的营养调节及其在 GH 分泌调节中的作用的一个令人信服的理由。