RELATION OF ACYL- AND DES-ACYL GHRELIN SECRETION AND PLASMA INSULIN, CORTISOL,GH

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。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 Ghrelin是一种肠源性酰化肽激素，其刺激生长激素（GH）和ACTH的分泌以及食欲。我们的中心论点是ghrelin保护哺乳动物免受饥饿：增加食欲和食物摄入;增加GH分泌以保护瘦体重;减少运动活动以保存卡路里;调节分配，包括葡萄糖稳态。该方案的总体假设是：（1）皮质醇和胰岛素是正常日常喂养模式和短期禁食期间生长激素释放肽释放的主要负调节剂;（2）肥胖改变了这种特定的控制机制，因此缺乏足够的生长激素释放肽抑制有助于暴饮暴食。我们的实验室已经开发了灵敏和特异性的夹心检测完整的活性酰基-ghrelin和去酰基ghrelin。使用这些分析，我们将确定脉冲式酰基和脱酰基ghrelin分泌和循环浓度的胰岛素，皮质醇和生长激素在健康瘦（胰岛素敏感）和肥胖（胰岛素抵抗）的成年人之间的时间关系。受试者将在进食和空腹（37.5小时）入院期间频繁采血（每10分钟一次，持续27小时）。这些结果将为预测其他直接控制ghrelin分泌的研究中直接干预的结果提供初步数据。它将确定皮质醇对生长激素释放肽分泌的影响，以确定其在生长激素释放肽分泌的昼夜变化中的作用。我们将确定胰岛素是否抑制生长素释放肽的分泌，以及葡萄糖相关的生长素释放肽抑制是否由胰岛素介导。

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 is a gut-derived acylated peptide hormone that stimulates secretion of growth hormone (GH) and ACTH, as well as orexigenesis. Our central thesis is that ghrelin protects mammals against starvation by: increasing appetite and food intake; increasing secretion of GH to protect lean body mass; decreasing locomotor activity to preserve calories; and regulating partitioning, including glucose homeostasis. The overall hypotheses of this protocol are: (1) cortisol and insulin are the dominant negative regulators of ghrelin release during normal daily patterns of feeding and short-term fasting; and (2) this specific control mechanism is altered by obesity, such that the lack of adequate ghrelin suppression contributes to overeating. Our laboratory has developed sensitive and specific sandwich assays for intact active acyl-ghrelin and des-acyl ghrelin. Using these assays, we will determine the temporal relationships between pulsatile acyl- and des-acyl ghrelin secretion and circulating concentrations of insulin, cortisol and GH in healthy lean (insulin sensitive) and obese (insulin resistant) adults. Subjects will have frequent blood sampling (every 10 min for 27 h) during fed and fasting (37.5 h) admissions. These results will provide the preliminary data for predicting the outcomes of direct interventions in other studies that will directly control ghrelin secretion. It will determine the effect of cortisol on ghrelin secretion to determine its role in diurnal variation in ghrelin secretion. We will determine whether insulin inhibits ghrelin secretion and whether glucose-related ghrelin suppression is mediated by insulin.