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

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 Ghrelin是一种主要来自胃的多肽，以活性(酰化)和非活性(去酰化)形式存在于血浆中。Ghrelin的主要活性形式含有28个氨基酸，具有独特的翻译后修饰：Ser3的羟基被辛酸酯化。正辛酰基是生长激素(GH)释放活性所必需的。血浆Ghrelin在能量平衡、食物摄取、生长激素释放和肥胖方面起着重要作用。到目前为止，还不清楚循环中的Ghrelin水平是如何受到调节的。在正常血糖条件下胰岛素对生长激素释放素水平的影响的研究得出了不一致的结果，即循环中的生长激素释放素减少或没有变化。目前也不清楚胰岛素抵抗的差异是否会影响胰岛素和/或葡萄糖对循环Ghrelin的影响。我们将研究正常血糖条件下胰岛素对两组体重指数匹配、具有不同胰岛素抵抗的年轻人外周Ghrelin的影响。使用我们实验室开发的分析方法，可以测量生物活性和非活性生长激素释放蛋白。 24例青年女性(低胰岛素抵抗组12例，高胰岛素抵抗组12例)和青年男性24例(低胰岛素抵抗组12例，高胰岛素抵抗组12例)(年龄18~30岁)进行了单盲安慰剂对照试验(BMI 18.5~35 kg/m2)。志愿者有3张入场券。正常血糖高胰岛素钳夹组2例(胰岛素输注速率分别为0.4mU/kg/min和1mU/kg/min)，对照组1例，用生理盐水代替胰岛素。在两组的体重指数匹配后，将比较胰岛素对酰基和去脂基生长激素的抑制作用。使用我们实验室开发的分析方法，可以测量生物活性和非活性生长激素释放蛋白。

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. 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 whether differences in insulin resistance have an impact on the effects of insulin and/or glucose on circulating ghrelin. We will examine the effects of insulin under euglycemic conditions on peripheral ghrelin in two groups of BMI matched young adults with different insulin resistance. Using assays developed in our laboratory, both bioactive and inactive ghrelin will be measured. For this purpose, twenty-four young women (n=12 in low insulin resistance group, n=12 in high insulin resistance group) and 24 young men (n=12 in low insulin resistance group, n=12 in high insulin resistance group), (ages 18-30 yrs) will be studied in a single-blind placebo-controlled experiment (BMI 18.5 to 35 kg/m2). The volunteers have 3 admissions. There are two euglycemic hyperinsulinemic clamp admissions (with 2 different insulin infusion rates: 0.4 mU/kg/min and 1 mU/kg/min) and one control admission which has a saline instead of an insulin infusion. The insulin induced suppression of acyl-and desacyl-ghrelin will be compared after the two groups have been matched for BMI. Using assays developed in our laboratory, both bioactive and inactive ghrelin will be measured.