EFFECT OF AGE ON INSULIN MEDIATED REGULATION OF GHRELIN

年龄对胰岛素介导的生长素释放肽调节的影响

• 批准号: 7718562
• 负责人: RALF M NASS
• 金额: $ 3.19万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-01 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7718562
• 关键词: Acute; Admission activity; Age; Amino Acids; Biological Assay; Computer Retrieval of Information on Scientific Projects Database; Condition; Eating; Elderly; Funding; Gender; Grant; Homeostasis; Infusion procedures; Institution; Insulin; Laboratories; Measures; Mediating; Obesity; Octanoic Acids; Peptides; Plasma; Play; Post-Translational Protein Processing; Protocols documentation; Purpose; Recruitment Activity; Regulation; Research; Research Personnel; Resources; Role; Saline; Somatotropin; Source; Stomach; Testing; United States National Institutes of Health; Woman; age effect; caprylic acid; des-n-octanoyl ghrelin; ghrelin; hydroxyl group; insulin sensitivity; men; volunteer; young adult

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Ghrelin, a peptide which is mainly derived from the stomach, is present in plasma in an active (acylated) and inactive (des-acylated) form. The major active form of ghrelin contains 28 amino acids with a unique post-translational modification: the hydroxyl group of ser3 is esterified by octanoic acid. The n-octanoyl group is essential for the growth hormone (GH) releasing activity. Plasma ghrelin plays a role in energy homeostasis, food intake, and possibly in GH release and obesity. To date, it is unclear how circulating ghrelin levels are regulated and whether there are age-specific differences in the regulation of ghrelin. Insulin sensitivity decreases with age. The studies proposed will investigate whether there are differences between young and older adults regarding the acute insulin mediated decrease in circulating ghrelin (bioactive, inactive form) levels. Insulin administered under euglycemic conditions will decrease circulating ghrelin levels to the same extent in older adults as in young adults when matched for BMI and insulin sensitivity. For this purpose, 24 men and women (12 of each gender) age 60 years and older will be recruited. The volunteers have 2 admissions. There is a euglycemic hyperinsulinemic clamp admission and a control admission which has a saline instead of an insulin infusion. The insulin induced suppression of acyl-and desacyl-ghrelin will be compared to a group of young men and women recruited and tested under a second protocol. Using assays developed in our laboratory, both bioactive and inactive ghrelin will be measured.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 生长素释放肽是一种主要源自胃的肽，以活性（酰化）和非活性（去酰化）形式存在于血浆中。生长素释放肽的主要活性形式包含 28 个氨基酸，具有独特的翻译后修饰：ser3 的羟基被辛酸酯化。正辛酰基对于生长激素 (GH) 释放活性至关重要。血浆生长素释放肽在能量稳态、食物摄入以及可能的生长激素释放和肥胖中发挥作用。迄今为止，尚不清楚循环中的生长素释放肽水平是如何调节的以及生长素释放肽的调节是否存在年龄特异性差异。胰岛素敏感性随着年龄的增长而降低。拟议的研究将调查年轻人和老年人之间在胰岛素介导的循环胃饥饿素（生物活性、非活性形式）水平急性降低方面是否存在差异。当体重指数和胰岛素敏感性相匹配时，在血糖正常的情况下注射胰岛素会降低老年人的循环生长素释放肽水平，其程度与年轻人相同。为此，将招募 24 名 60 岁及以上的男性和女性（男女各 12 名）。录取志愿者2人。有正常血糖高胰岛素钳夹入院和对照入院，其中用盐水代替胰岛素输注。胰岛素诱导的酰基和去酰基生长素释放肽的抑制将与根据第二个方案招募和测试的一组年轻男性和女性进行比较。使用我们实验室开发的检测方法，将测量生物活性和非活性的生长素释放肽。