MENTORED PATIENT-ORIENTED RESEARCH CAREER DEVELOPMENT AWARD

Ghrelin是一种主要来自胃的多肽，以活性(酰化)和非活性形式存在于血浆中。 (去酰化)形式。Ghrelin的主要活性形式包含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所必需的 (生长激素)释放活性。血浆Ghrelin在能量平衡、食物摄入中起作用，可能在生长激素中起作用。 释放和肥胖。到目前为止，还不清楚循环中的Ghrelin水平是如何受到调节的。对此的总体假设是 葡萄糖、胰岛素以及胰岛素敏感性在Ghrelin的急性调节中起着重要作用。的影响 此外，还将研究年龄和体重指数对循环中生长激素对这些因素的反应。 具体目标1.确定Ghrelin的短期调节在多大程度上是通过葡萄糖介导的 (外周或腔内)和/或外周胰岛素。在人类中，葡萄糖后循环中的胃促生长素水平下降 行政管理。目前尚不清楚葡萄糖的给药途径在多大程度上影响其对循环的影响。 生长激素释放素。正常血糖条件下胰岛素对胃促生长素水平影响的研究得出了不一致的结果，即 与无变化相比，循环中生长激素减少。目前也不清楚葡萄糖给药途径在多大程度上起到了作用 在其对循环Ghrelin的影响中的作用以及胰岛素抵抗的差异是否影响 胰岛素和/或葡萄糖对循环Ghrelin的影响。在两组中，体重指数与不同胰岛素的年轻人相匹配 ，我们将研究正常血糖条件下胰岛素对外周Ghrelin的影响，并对它们进行比较 具有口服和静脉注射葡萄糖的效果。我们还将比较口服和静脉注射葡萄糖对外周Ghrelin的影响 彼此之间。静脉注射后达到的血糖水平将与口服葡萄糖测试时达到的水平相匹配。 胰岛素和葡萄糖对Ghrelin生物活性的影响尚未见报道。使用我们开发的分析方法 实验室，将测量生物活性和非活性Ghrelin 具体目的2.确定胰岛素介导的循环生长激素水平下降是否与年龄有关 依附的。胰岛素敏感性随年龄增长而降低。这在一定程度上是由于腹部的年龄相关性增加所致。 内脏脂肪。建议的研究将调查年轻人和老年人之间是否存在差异 关于急性胰岛素介导的循环Ghrelin(生物活性、非活性形式)水平的下降。

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 GH (growth hormone) 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. The overall hypothesis of this grant is that glucose, insulin as well as insulin sensitivity play a role in the acute regulation of ghrelin. The influence of age and BMI on the response of circulating ghrelin to these factors will also be examined. Specific Aim 1. To determine to what extent the short-term regulation of ghrelin is mediated through glucose (peripheral or luminal) and/or peripheral insulin. In man, circulating ghrelin levels decrease after glucose administration. It is unclear to what extent the route of glucose administration plays a role in its effects on circulating ghrelin. 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 to what extent the route of glucose administration plays a role in its effects on circulating ghrelin and whether differences in insulin resistance have an impact on the effects of insulin and/or glucose on circulating ghrelin. In two groups of BMI matched young adults with different insulin resistance, we will examine the effects of insulin under euglycemic conditions on peripheral ghrelin and compare them with the effects of oral and IV glucose. We will also compare the effects of oral and IV glucose on peripheral ghrelin with each other. The glucose levels reached after IV administration will match those reached during the oral glucose test. The effects of insulin and glucose on bioactive ghrelin have not been reported. Using assays developed in our laboratory, both bioactive and inactive ghrelin will be measured Specific Aim 2. To determine whether the insulin-mediated decrease in circulating ghrelin levels is age dependent. Insulin sensitivity decreases with age. This is partially a result of the age-dependent increase in abdominal visceral fat. The studies proposed will investigate whether there are differences between young and older adults regarding the acute insulin mediated decrease in circulating ghrelin (bioactive, inactive form) levels.