MENTORED PATIENT-ORIENTED RESEARCH CAREER DEVELOPMENT AWARD

以患者为导向的研究职业发展奖

• 批准号: 7649412
• 负责人: RALF M NASS
• 金额: $ 13.13万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-22 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7649412
• 关键词: Abdomen; Acute; Age; Amino Acids; Biological Assay; Body Composition; Eating; Elderly; Fasting; Fatty acid glycerol esters; Glucose; Grant; Homeostasis; Infusion procedures; Insulin; Insulin Resistance; Intervention; Laboratories; Measures; Mediating; Mentored Patient-Oriented Research Career Development Award; Obesity; Octanoic Acids; Oral; Peptides; Peripheral; Physiological; Plasma; Play; Post-Translational Protein Processing; Regulation; Reporting; Role; Route; Somatotropin; Stomach; Testing; Visceral; age related; ghrelin; hydroxyl group; insulin sensitivity; man; response; young adult

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 GH (growth hormone) 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. The overall hypothesis of this grant is that glucose, insulin as well as insulin sensitivity play a role in the acute regulation of ghrelin. The influence of age and BMI on the response of circulating ghrelin to these factors will also be examined. Specific Aim 1. To determine to what extent the short-term regulation of ghrelin is mediated through glucose (peripheral or luminal) and/or peripheral insulin. In man, circulating ghrelin levels decrease after glucose administration. It is unclear to what extent the route of glucose administration plays a role in its effects on circulating ghrelin. Studies of insulin effects on ghrelin levels under euglycemic conditions have yielded inconsistent results, i.e., a decrease in circulating ghrelin vs. no change. It is also unclear to what extent the route of glucose administration plays a role in its effects on circulating ghrelin and whether differences in insulin resistance have an impact on the effects of insulin and/or glucose on circulating ghrelin. In two groups of BMI matched young adults with different insulin resistance, we will examine the effects of insulin under euglycemic conditions on peripheral ghrelin and compare them with the effects of oral and IV glucose. We will also compare the effects of oral and IV glucose on peripheral ghrelin with each other. The glucose levels reached after IV administration will match those reached during the oral glucose test. The effects of insulin and glucose on bioactive ghrelin have not been reported. Using assays developed in our laboratory, both bioactive and inactive ghrelin will be measured Specific Aim 2. To determine whether the insulin-mediated decrease in circulating ghrelin levels is age dependent. Insulin sensitivity decreases with age. This is partially a result of the age-dependent increase in abdominal visceral fat. 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.

在活性（酰化）和非活性中，血浆中存在主要源自胃中的肽 （Des-acylated）形式。生长素蛋白的主要活性形式含有28种具有独特后翻译后的氨基酸 修饰：Ser3的羟基通过辛酸酯化。 n- octanoyl群对于GH至关重要 （生长激素）释放活性。血浆生长素素在能量稳态，食物摄入量以及可能在GH中发挥作用 释放和肥胖。迄今为止，尚不清楚如何调节流循环的生长素素水平。总体假设 Grant是葡萄糖，胰岛素和胰岛素敏感性在生长素蛋白的急性调节中起作用。影响 还将检查年龄和BMI对循环生长素对这些因素的反应的反应。 具体目的1。确定葡萄糖的短期调节在多大程度上 （外围或腔内）和/或外周胰岛素。在人类中，葡萄糖后循环的生长素释放水平降低 行政。目前尚不清楚葡萄糖给药的途径在多大程度上在其对循环的影响中起作用 ghrelin。胰岛素对在葡萄糖疾病下的胰岛素作用的研究产生了不一致的结果，即A 减少循环发芽肽与无变化的减少。目前尚不清楚葡萄糖给药的途径在多大程度上 在其对循环生长素蛋白的影响以及胰岛素抵抗的差异中的作用是否会影响 在循环的生长素蛋白上胰岛素和/或葡萄糖。在两组BMI中，与不同的胰岛素相匹配 耐药性，我们将检查胰岛素条件下胰岛素对外周生长素蛋白的影响并进行比较 与口服和静脉葡萄糖的作用。我们还将比较口服和静脉葡萄糖对外周生长素蛋白的影响 彼此。静脉输送后达到的葡萄糖水平将与口服葡萄糖测试期间达到的葡萄糖水平相匹配。 胰岛素和葡萄糖对生物活性生长素蛋白的影响尚未报道。使用我们在我们的 实验室将测量生物活性和非活性生长素 具体目的2。确定胰岛素介导的循环生长素素水平的降低是年龄 依赖。胰岛素灵敏度随着年龄的增长而降低。这部分是由于年龄依赖性腹部增加的结果 内脏脂肪。提出的研究将研究年轻人和老年人之间是否存在差异 关于急性胰岛素介导的循环发芽素（生物活性，非活性形式）水平的降低。