EFFECT OF AGE ON INSULIN MEDIATED REGULATION OF GHRELIN

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是一种主要来自胃的多肽，以活性(酰化)和非活性(去酰化)形式存在于血浆中。Ghrelin的主要活性形式含有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(GH)释放活性所必需的。血浆Ghrelin在能量平衡、食物摄取、生长激素释放和肥胖方面起着重要作用。到目前为止，还不清楚血液中的Ghrelin水平是如何调节的，也不清楚在调节Ghrelin方面是否存在年龄差异。胰岛素敏感性随年龄增长而降低。建议的研究将调查年轻人和老年人在胰岛素介导的急性循环Ghrelin(生物活性、非活性形式)水平下降方面是否存在差异。在体重指数和胰岛素敏感性匹配的情况下，在正常血糖条件下给予胰岛素将降低老年人的血液中生长激素水平，其程度与年轻人相同。为此，将招聘年龄在60岁及以上的24名男性和女性(男女各12名)。志愿者有两张入场券。有正常血糖高胰岛素钳夹入院和对照入院，后者用生理盐水代替胰岛素输注。胰岛素诱导的酰基和去脂基Ghrelin的抑制将与一组年轻的男性和女性进行比较，并在第二种方案下进行测试。使用我们实验室开发的分析方法，可以测量生物活性和非活性生长激素释放蛋白。

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 and whether there are age-specific differences in the regulation of ghrelin. Insulin sensitivity decreases with age. 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. Insulin administered under euglycemic conditions will decrease circulating ghrelin levels to the same extent in older adults as in young adults when matched for BMI and insulin sensitivity. For this purpose, 24 men and women (12 of each gender) age 60 years and older will be recruited. The volunteers have 2 admissions. There is a euglycemic hyperinsulinemic clamp admission and a control admission which has a saline instead of an insulin infusion. The insulin induced suppression of acyl-and desacyl-ghrelin will be compared to a group of young men and women recruited and tested under a second protocol. Using assays developed in our laboratory, both bioactive and inactive ghrelin will be measured.