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

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。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。重组人生长激素（rhGH）治疗可降低低血糖风险，降低胰岛素敏感性。我们假设，当GHD儿童与健康对照组相比时，GHD导致来自血管生成的葡萄糖分数减少，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，用rhGH治疗8周的GDH受试者将具有源自糖原异生的葡萄糖分数的增加和糖原分解形式的减少以及胰岛素敏感性降低。为了检验这一假设，将使用稳定同位素[U-13 C]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。我们将专门测量过夜禁食后的葡萄糖生成率、糖原生成率、糖原分解率、胰岛素敏感性和胰高血糖素反应率。此外，我们将使用稳定同位素[15 N2]尿素、[1- 13 C]亮氨酸以及游离脂肪酸和b-羟基丁酸盐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rhGH治疗8周后进行研究。

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.