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的一个 由NIH/NCRR资助的中心赠款提供的资源。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，不一定是研究者的机构。 Ghrelin是一种主要来源于胃的肽，以活性（酰化）和非活性（去酰化）形式存在于血浆中。生长激素释放肽的主要活性形式包含28个氨基酸，具有独特的翻译后修饰：丝氨酸3的羟基被辛酸酯化。正辛酰基对于生长激素（GH）释放活性是必需的。血浆ghrelin在能量稳态、食物摄入中起作用，并且可能在GH释放和肥胖中起作用。到目前为止，还不清楚循环ghrelin水平是如何调节的。在血糖正常条件下胰岛素对胃饥饿素水平影响的研究产生了不一致的结果，即，循环胃饥饿素的减少与没有变化。目前还不清楚胰岛素抵抗的差异是否对胰岛素和/或葡萄糖对循环ghrelin的作用有影响。我们将研究正常血糖条件下胰岛素对两组BMI匹配的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测定法，将测量生物活性和非活性ghrelin。 为此，将在单盲安慰剂对照实验（BMI 18.5至35 kg/m2）中研究24名年轻女性（低胰岛素抵抗组n = 12，高胰岛素抵抗组n = 12）和24名年轻男性（低胰岛素抵抗组n=12，高胰岛素抵抗组n=12）（年龄18-30岁）。志愿者有3个名额。有两个正常血糖高胰岛素钳夹入院（2种不同的胰岛素输注速率：0.4 mU/kg/min和1 mU/kg/min）和一个对照入院，其使用生理盐水代替胰岛素输注。在两组BMI匹配后，将比较胰岛素诱导的酰基-和去酰基-ghrelin抑制。使用我们实验室开发的测定法，将测量生物活性和非活性ghrelin。

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.