ACTIONS OF MELANOCORTIN AGONISTS IN OBESE PRIMATES

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 MC 4受体被认为是最有效的促凋亡系统之一，因此是备受追捧的药物靶标。 这个系统似乎在从鱼类到人类的许多物种中都是保守的。 然而，这个目标也有很大的潜在心血管副作用。 本研究的目的是研究一种新的MC 4类似物，以1）验证该化合物的功效，并表明其可对肥胖糖尿病前期猴的体重和葡萄糖稳态产生有效影响; 2）研究潜在的心血管副作用和治疗窗。 这些先前研究的结果已经被写进了一份手稿，我们预计很快就会提交。这些新的研究旨在进一步的临床研究，以确定具有最高疗效且无显著心血管并发症（血压或心率）的制剂。 此外，这些研究使用来自肥胖NHP资源的动物。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The MC4 receptor is considered to be one of the most potent anorexigenic systems and thus a highly sought after drug target. This system appears to be conserved across many species from fish to humans. However, this target also has great potential for cardiovascular side effects. The purpose of this study is to investigate a novel MC4 analog to 1) validate the efficacy of this compound and show that it can have potent effects body weight and glucose homeostasis in obese prediabetic monkeys; and 2) to investigate potential cardiovascular side effects and therapeutic window. The results from these previous studies have been written into a manuscript that we expect to submit soon. These new studies are designed to further clinical studies to identify formulations that have the highest efficacy with no significant cardiovascular complications (blood pressure or heart rate). Furthermore, these studies used animals from the Obese NHP Resource.