THE IMPACT OF INSULIN ON THE SHORT-TERM REGULATION OF GHRELIN

胰岛素对 GHRELIN 短期调节的影响

• 批准号: 8167173
• 负责人: RALF M NASS
• 金额: $ 10.02万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-01 至 2013-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8167173
• 关键词: Acute; Admission activity; Age; Amino Acids; Biological Assay; Computer Retrieval of Information on Scientific Projects Database; 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; Recruitment Activity; Regulation; Research; Research Personnel; Resources; Role; Saline; Somatotropin; Source; Stomach; Testing; United States National Institutes of Health; Woman; des-n-octanoyl ghrelin; ghrelin; hydroxyl group; insulin sensitivity; men; volunteer; waist circumference; 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. We hypothesize that insulin administered under euglycemic conditions will decrease ghrelin to a lesser extent in older adults when compared to young adults. 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, waist circumference 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 another protocol. Using assays developed in the investigators' laboratory, both bioactive and inactive ghrelin will be measured.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 Ghrelin是一种主要来源于胃的肽，以活性（酰化）和非活性（去酰化）形式存在于血浆中。生长激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：丝氨酸3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ghrelin在能量稳态、食物摄入中起作用，并且可能在GH释放和肥胖中起作用。迄今为止，尚不清楚循环ghrelin水平是如何调节的，以及ghrelin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下降。拟议的研究将调查年轻人和老年人之间是否存在关于急性胰岛素介导的循环ghrelin（生物活性，非活性形式）水平降低的差异。我们推测，与年轻人相比，在血糖正常的情况下使用胰岛素会在较小程度上降低老年人的ghrelin。 在正常血糖条件下给予胰岛素将使老年人的循环ghrelin水平降低到与BMI、腰围和胰岛素敏感性匹配的年轻人相同的程度。为此，将招募24名60岁及以上的男女（男女各12人）。志愿者有两个入场券。有一个正常血糖高胰岛素钳夹入院和一个对照入院，对照入院用盐水代替胰岛素输注。胰岛素诱导的酰基和去酰基ghrelin的抑制将与另一方案招募和测试的一组年轻男性和女性进行比较。使用研究者实验室开发的测定法，将测量生物活性和非活性ghrelin。