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Stomach Ghrelin Homeostasis in Aging

衰老过程中胃饥饿素稳态

基本信息

批准号：
6883154
负责人：
GEORGE H GREELEY
金额：
$ 7.55万
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：
2004
资助国家：
美国
起止时间：
2004-04-15 至 2006-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6883154
关键词：
body weight cholecystokinin gastrointestinal hormones ghrelin glucagon growth hormone releasing hormone hormone regulation /control mechanism immunocytochemistry in situ hybridization laboratory rat nutrient intake activity nutrition of aging nutrition related tag radioimmunoassay secretion somatotropin western blottings

项目摘要

RESEARCH TOPIC: #18 - Functional Senescence in the aging population, growth hormone (GH) secretion and nutrition are compromised. GH is an essential hormone that regulates nearly every tissue in the body. Aging associated declines in GH secretion and nutrition may contribute significantly to reductions in overall physical and mental function and ability to tolerate stress insults. Our long-term goal is to identify new clinical approaches that avert deterioration in GH iecretion and nutritional intake in aging humans. Emerging evidence supports the hypothesis that pituitary GH secretion is regulated not only by GH releasing hormone (GHRH) from the hypothalamus, but also by ghrelin from the stomach. Ghrelin is a new stomach hormone that stimulates GH secretion, food intake, adiposity and weight gain. Our long-term, working hypotheses are that stomach ghrelin is a key player in linking the gastrointestinal system, i.e., nutritional intake with regulation of GH secretion, maintenance of body weight and growth, and that the stomach ghrelin-pituitary GH axis is compromised by the aging process. For this proposal, our hypothesis is that regulation of stomach ghrelin production and secretion by the intestinal hormone cholecystokinin (CCK) and pancreatic glucagon is altered by the aging process. Preliminary findings implicate a stomach-ghrelin pituitary GH axis that is influenced by dietary intake and the gut-pancreatic hormones, CCK and glucagon. Our Specific Aims are: Aim 1. To test the hypothesis that the ging process alters the regulation of pituitary GH secretion by ghrelin. Aim 2. To test the hypothesis that ging associated elevations in stomach ghrelin homeostasis are activated mechanistically by alterations in regulation by glucagon and cholecystokinin (CCK). This research is significant because we will identify mechanisms underlying regulation of GH secretion by omach ghrelin and the role of nutrition and nutritionally activated hormones in the regulation of GH secretion. This research will open up new therapeutic strategies for treatment of diseases of aging in which weight loss or gain plays a critical role. This is a compelling reason to define nutritional regulation of ghrelin and its role ingulation of GH secretion, weight gain and growth.

研究主题：#18 -功能性衰老在老龄人口中，生长激素（GH）分泌和营养受到损害。GH是一个一种调节身体几乎每一个组织的基本激素。衰老相关的生长激素分泌和营养的下降可能会显着减少整体的身体和精神功能和能力，以承受压力的侮辱。我们的长期目标是确定新的临床方法，以避免在生长激素分泌和营养摄入老化的人恶化。越来越多的证据支持这一假设，即垂体GH分泌不仅受到来自下丘脑的GH释放激素（GHRH）的调节，而且还受到来自胃的ghrelin的调节。Ghrelin是一种新的胃激素，刺激GH分泌，食物摄入，肥胖和体重增加。我们的长期工作假设是胃饥饿素是连接胃肠道系统的关键因素，即，营养摄入与生长激素分泌的调节，维持体重和生长，以及胃生长激素释放肽-垂体生长激素轴是由老化过程中受到损害。对于这一建议，我们的假设是，调节胃生长素的生产和分泌的肠激素胆囊收缩素（CCK）和胰高血糖素是改变了老化过程。初步研究结果表明，胃-脑垂体生长激素轴受饮食摄入和肠-胰腺激素、CCK和胰高血糖素的影响。我们的具体目标是：目标1。验证生长过程改变了ghrelin对垂体生长激素分泌的调节这一假说。目标2.为了验证与胃饥饿相关的胃饥饿素稳态升高是通过胰高血糖素和胆囊收缩素（CCK）调节的改变而机制性激活的假设。这项研究是重要的，因为我们将确定潜在的机制调节生长激素分泌的omach生长激素释放肽和营养和营养激活激素的作用，在调节生长激素分泌。这项研究将为治疗衰老疾病开辟新的治疗策略，其中体重减轻或增加起着关键作用。这是一个令人信服的理由来定义生长激素释放肽的营养调节和它的作用ingulation生长激素分泌，体重增加和增长。