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是一种肠源性酰化多肽激素，可刺激生长激素(GH)和促肾上腺皮质激素释放激素(ACTH)的分泌，以及食欲。我们的中心论点是，Ghrelin通过以下方式保护哺乳动物免受饥饿：增加食欲和食物摄入量；增加GH的分泌以保护瘦体重；减少运动活动以保存卡路里；以及调节分配，包括葡萄糖动态平衡。该方案的总体假设是：(1)在正常的日常进食模式和短期禁食期间，皮质醇和胰岛素是生长激素释放的主要负调节因素；(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抑制导致暴饮暴食。我们的实验室已经建立了灵敏和特异的完整活性酰基Ghrelin和去酰基Ghrelin的夹心检测方法。使用这些检测方法，我们将确定健康瘦(胰岛素敏感)和肥胖(胰岛素抵抗)成年人的搏动性酰基和去酰基生长激素分泌与胰岛素、皮质醇和生长激素循环浓度之间的时间关系。受试者将在进食和禁食(37.5小时)入院期间进行频繁的血液采样(每10分钟一次，持续27小时)。这些结果将为预测直接控制Ghrelin分泌的其他研究中直接干预的结果提供初步数据。它将确定皮质醇对Ghrelin分泌的影响，以确定其在Ghrelin分泌的日变化中的作用。我们将确定胰岛素是否抑制Ghrelin的分泌，以及葡萄糖相关的Ghrelin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.