Regulation of Stomach Ghrelin

胃饥饿素的调节

• 批准号: 6771666
• 负责人: GEORGE H GREELEY
• 金额: $ 30.55万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6771666
• 关键词: RNase protection assay; capsaicin; cholecystokinin; clinical research; dietary proteins; endocrine pharmacology; enzyme feedback; fasting; genetic regulatory element; genetic transcription; glucagon; homeostasis; hormone biosynthesis; hormone receptor; hormone regulation /control mechanism; immunocytochemistry; in situ hybridization; insulinlike growth factor; laboratory rat; nutrient intake activity; peptide hormone; receptor expression; secretion; somatotropin; stomach

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Ghrelin是生长激素(GH)神经内分泌轴的营养状态的关键信号，起着整合能量平衡和生长过程的作用。这项研究的主要目的是确定胃Ghrelin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Ghrelin的表达和分泌受饮食、胃肠道和胰腺激素的调节，并且存在胃Ghrelin-垂体GH轴。我们的具体目标是：1.验证胃促生长素在调节垂体GH分泌中的作用；垂体GH和胃GH分泌之间存在双向反馈环；Ghrelin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Ghrelin分泌和Ghrelin激活的GH分泌。目的2.验证胃促生长素稳态受胆囊收缩素(CCK)、胰高血糖素和胰岛素样生长因子-1(IGF-I)调节的假说。目的3.鉴定大鼠和人类Ghrelin基因的调控元件，并验证调节元件对生长激素、胰升糖素和营养素的响应假设。根据初步研究结果，我们有望证明内源性胃促生长素参与胃促生长素分泌的调节，生长激素对胃促生长素的分泌起反馈作用，胃促生长素-生长激素轴受饮食摄入量的调节；胃促生长素的动态平衡受CCK、胰高血糖素和IGF-I的调节；以及生长激素基因的启动子活性(即胃促生长素的产生)受生长激素、胰升糖素和营养素的调节。营养状况对于预测各种分解代谢性疾病和Lrauma的存活率至关重要。这项研究意义重大，因为我们的研究将阐明Ghrelin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。这是一个令人信服的理由来定义Ghrelin生产和分泌的营养调节及其在GH分泌调节中的作用。