DOES RYGB ALTER CIRCULATING GUT-DERIVED PEPTIDES IN MORBIDLY OBESE PATIENTS

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。次级项目的主要支助 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。 肥胖与许多医学疾病有关，其中最具破坏性的是糖尿病（T2 DM）。超过1500万美国人患有T2 DM，这是终末期肾病、失明和非创伤性截肢的主要原因。最近的证据表明RYGB是T2 DM患者最有效的治疗方法。RYGB后，超过80%的肥胖患者的T2 DM消退。RYGB后T2 DM的改善似乎是肠道解剖结构变化的结果，这些变化影响肠道代谢和内分泌功能。尽管有这一重要的观察结果，我们目前对肠道解剖结构的变化如何改善T2 DM的理解是有限的。我们假设，对T2 DM患者RYGB前后空腹和餐后血浆的蛋白质组学分析将增强我们对肠道解剖结构变化如何改善T2 DM的理解。基于我们已建立的包含纵向RYGB前后组织样本的组织库，我们处于与PNNL合作并进行这些研究的独特位置。此外，RYGB前后患者空腹血浆的初步蛋白质组学分析支持这一假设，并提供了概念证明。拟议的研究有可能极大地影响我们对RYGB如何改善T2 DM的理解，并可能发现新的医学疗法。此外，我们预计他们将为未来的研究确定潜在的介质，为未来的拨款提交和科学数据的出版产生初步数据。

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. Obesity is associated with numerous medical conditions, the most devastating of which is diabetes (T2DM). Ove 15 million Americans are afflicted with T2DM which represents the leading cause of end-stage renal disease, blindness, and non-traumatic limb amputation. Recent evidence suggests RYGB to be the most effective treatment available for patients with T2DM. Resolution of T2DM is noted in over 80% of obese patients after RYGB. Post-RYGB improvements in T2DM appear to be the result of changes in gut anatomy which influence intestinal metabolism and endocrine function. Despite this important observation, our current understanding of how changes in gut anatomy improve T2DM is limited. We hypothesize that proteomic analyses of pre- and post-RYGB fasting and post-prandial plasma in patients ¿ T2DM will enhance our understanding of how changes in gut anatomy improve T2DM. Based on our established tissue bank containing longitudinal pre- and post-RYGB tissue samples we are in a unique position to collaborate with PNNL and perform these studies. Furthermore, preliminary proteomic analysis of fasting plasma from pre- and post-RYGB patients support this hypothesis and provide proof of concept. The proposed studies have the potential to dramatically influence our understanding of how RYGB improves T2DM and potentially identify new medical therapies. In addition we anticipate they will identify potential mediators for future study, generate preliminary data for future grant submission and scientific data for publication.