EFFECTS OF GROWTH HORMONE THERAPY ON GLUCOSE AND PROTEIN METABOLISM IN CHILDR

生长激素治疗对儿童葡萄糖和蛋白质代谢的影响

• 批准号: 7605861
• 负责人: MOREY W HAYMOND
• 金额: $ 0.26万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-02-15 至 2007-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7605861
• 关键词: Amino Acids; Child; Computer Retrieval of Information on Scientific Projects Database; Diagnosis; Funding; Glucagon; Gluconeogenesis; Glucose; Grant; Growth; Hydroxybutyrates; Hypoglycemia; Institution; Isotopes; Leucine; Measures; Newly Diagnosed; Nonesterified Fatty Acids; Production; Protein Biosynthesis; Proteins; Proteolysis; Rate; Research; Research Personnel; Resources; Risk; Somatotropin; Source; Testing; Time; United States National Institutes of Health; Urea; Week; abstracting; glucose production; glycogenolysis; growth hormone deficiency; hormone therapy; infancy; insulin sensitivity; lipid metabolism; oxidation; protein metabolism; r-hGH-M; response; stable isotope

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. ABSTRACT Children with growth hormone deficiency (GHD) have increased insulin sensitivity and may present with hypoglycemia during infancy. Treatment with recombinant human growth hormone (rhGH) reduces the risk for hypoglycemia and decreases insulin sensitivity. We hypothesize, that GHD causes a decrease in the fraction of glucose derived form gluconeogenesis and conversely glycogenolysis and insulin sensitivity will be increased, when GHD children are compared to healthy controls. We anticipate that total glucose production will be unaffected by rhGH therapy. Therefore, the GDH subjects treated with rhGH for 8 weeks will have an increase in the fraction of glucose derived form gluconeogenesis and a decrease in that form glycogenolysis and decreased insulin sensitivity. To test this hypothesis, 10 healthy and 10 GHD children will be studied using the stable isotope [U-13C] glucose and Mass Isotopes Distribution Analysis (MIDA). We will be specifically measuring the rate of glucose production, gluconeogenesis, glycogenolysis, insulin sensitivity and glucagon response after an overnight fast. In addition, we will measure changes in protein oxidation, proteolysis and fat metabolism using the stable isotopes [15N2] urea, [1-13C] leucine and concentrations of free fatty acids and b-hydroxybutyrate. The GHD group will be studied at the time of diagnosis and after 8 weeks of rhGH. HYPOTHESIS H1- The fraction of glucose derived from gluconeogenesis is decreased and that from glycogenolysis is increased in the post-absorptive state in untreated GHD children when compared to healthy children. H2- Treatment with rhGH will not change the overall glucose turnover but will normalize the abnormal partitioning of gluconeogenesis and glycogenolysis in GHD children. H3- GH replacement will reduce urea production and increase estimates of protein synthesis, thus optimizing the availability of amino acids for growth. H4- Untreated children with GHD after an overnight fast will have an increased glucagon challenge response that will decrease after 8 weeks of treatment with rhGH. SPECIFIC AIMS In healthy and newly diagnosed GHD children we will: 1. Measure the Glucose Production Rate (GPR) 2. Determine the fraction of glucose derived from gluconeogenesis and glycogenolysis 3. Estimate insulin sensitivity 4. Measure proteolysis and protein oxidation 5. Determine glucagon challenge response after an overnight fast. The above-mentioned parameters will be re-evaluated in the children with GHD after 8 weeks of rhGH therapy.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 抽象的 生长激素缺乏症（GHD）的儿童具有胰岛素敏感性的提高，并且在婴儿期可能患有低血糖。重组人类生长激素（RHGH）治疗可降低低血糖的风险并降低胰岛素敏感性。 我们假设，GHD会导致葡萄糖衍生的葡萄糖生成的比例减少，相反，当将GHD儿童与健康对照组进行比较时，将会提高糖原分解和胰岛素敏感性。 我们预计总葡萄糖的总产生将不受RHGH治疗的影响。因此，用RHGH处理的GDH受试者8周将增加葡萄糖衍生的糖异生的比例，并减少该形式的糖原分解和胰岛素敏感性降低。为了检验这一假设，将使用稳定的同位素[U-13C]葡萄糖和群众同位素分布分析（MIDA）研究10名健康和10名GHD儿童。 在快速过夜后，我们将专门测量葡萄糖产生，糖原生成，糖原溶解，胰岛素敏感性和胰高血糖素反应的速率。此外，我们将使用稳定的同位素[15N2]尿素，[1-13C]亮氨酸和游离脂肪酸和B-羟基丁酸酸酯的浓度来衡量蛋白质氧化，蛋白水解和脂肪代谢的变化。 GHD组将在诊断时和RHGH 8周后进行研究。 假设 H1-与健康儿童相比，未经治疗的GHD儿童的吸收后状态中，从糖异生中得出的葡萄糖的比例降低了。 H2-用RHGH治疗不会改变总体葡萄糖更新，而是将GHD儿童中糖异生和糖基解分解的异常分配。 H3- GH替代将减少尿素的产生并增加蛋白质合成的估计值，从而优化氨基酸的生长可用性。 H4-未经治疗的GHD过夜后的儿童将增加胰高血糖素的挑战反应，在使用RHGH治疗8周后会减少。 具体目标 在健康，新诊断的GHD儿童中，我们将： 1。测量葡萄糖生产率（GPR） 2。确定葡萄糖生成和糖原分解的葡萄糖的分数 3。估计胰岛素敏感性 4。测量蛋白水解和蛋白质氧化 5。快速过夜后确定胰高血糖素挑战反应。 在RHGH治疗8周后，将在GHD儿童中重新评估上述参数。