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

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 生长素释放肽是一种肠道来源的酰化肽激素，可刺激生长激素 (GH) 和 ACTH 的分泌以及食欲生成。我们的中心论点是，生长素释放肽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，包括葡萄糖稳态。该协议的总体假设是：（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素释放肽释放的主要负调节剂； (2)这种特定的控制机制会因肥胖而改变，因此缺乏足够的生长素释放肽抑制会导致暴饮暴食。我们的实验室开发了针对完整活性酰基生长素释放肽和去酰基生长素释放肽的灵敏且特异的夹心测定法。使用这些测定，我们将确定健康瘦（胰岛素敏感）和肥胖（胰岛素抵抗）成年人中脉动酰基和去酰基生长素释放肽分泌与胰岛素、皮质醇和生长激素循环浓度之间的时间关系。受试者在进食和禁食（37.5 小时）入院期间将频繁进行血液采样（27 小时内每 10 分钟一次）。这些结果将为预测其他直接控制生长素释放肽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素释放肽分泌的影响，以确定其在生长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.