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

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。患有生长激素缺乏症（GHD）的儿童胰岛素敏感性增加，并可能在婴儿期出现低血糖。用重组人生长激素（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，当GHD儿童与健康对照比较时，GHD导致糖异生产生的葡萄糖比例减少，相反糖原分解和胰岛素敏感性将增加。我们预计总葡萄糖产量将不受rhGH治疗的影响。因此，接受rhGH治疗8周的GDH受试者将出现糖异生形式的葡萄糖含量增加，糖原溶解形式的葡萄糖含量减少，胰岛素敏感性降低。为了验证这一假设，将使用稳定同位素[U-13C]葡萄糖和质量同位素分布分析（MIDA）对10名健康儿童和10名GHD儿童进行研究。我们将在一夜禁食后具体测量葡萄糖生成、糖异生、糖原溶解、胰岛素敏感性和胰高血糖素反应的速率。此外，我们将使用稳定同位素[15N2]尿素，[1-13C]亮氨酸以及游离脂肪酸和b-羟基丁酸的浓度来测量蛋白质氧化，蛋白质水解和脂肪代谢的变化。GHD组将在诊断时和8周rhGH后进行研究。

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. 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.