Stomach Ghrelin Homeostasis in Aging

衰老过程中胃饥饿素稳态

• 批准号: 6720572
• 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
• 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/6720572
• 关键词: body weight; cholecystokinin; gastrointestinal hormones; 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

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 在人口老龄化中，生长激素（GH）的分泌和营养受到损害。 GH 是一个 调节身体几乎每个组织的必需激素。与衰老相关的 GH 分泌和营养下降可能会显着导致整体身心功能以及承受压力损伤的能力下降。我们的长期目标是找到新的临床方法，避免老年人的 GH 分泌和营养摄入恶化。 新出现的证据支持这样的假设：垂体 GH 分泌不仅受到下丘脑的 GH 释放激素 (GHRH) 的调节，还受到胃的生长素释放肽的调节。胃饥饿素是一种新型胃激素，可刺激 GH 分泌、食物摄入、肥胖和体重增加。我们的长期有效假设是，胃生长素释放肽在连接胃肠系统（即营养摄入与调节 GH 分泌、维持体重和生长）方面发挥着关键作用，并且胃生长素释放肽-垂体 GH 轴因衰老过程而受到损害。 对于这一提议，我们的假设是，肠道激素胆囊收缩素 (CCK) 和胰高血糖素对胃生长素释放肽产生和分泌的调节会因衰老过程而改变。初步研究结果表明，胃-生长素释放肽-垂体 GH 轴受到饮食摄入量和肠-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. 检验 Ging 过程改变 ghrelin 对垂体 GH 分泌的调节这一假设。目标 2. 检验以下假设：与胃饥饿素稳态升高相关的 Ging 是通过胰高血糖素和胆囊收缩素 (CCK) 调节的改变而机械激活的。 这项研究意义重大，因为我们将确定 omach ghrelin 调节 GH 分泌的潜在机制，以及营养和营养激活激素在 GH 分泌调节中的作用。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。这是定义生长素释放肽的营养调节及其对 GH 分泌、体重增加和生长的调节作用的一个令人信服的理由。