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

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 肥胖与许多疾病有关，其中最具破坏性的是糖尿病(T2 DM)。超过1500万美国人患有2型糖尿病，它是导致终末期肾病、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患者可用的最有效的治疗方法。在RYGB治疗后，超过80%的肥胖者T2 DM的消退。RYGB术后T2 DM的改善似乎是肠道解剖改变的结果，这些改变影响了肠道代谢和内分泌功能。尽管有这些重要的观察，但我们目前对肠道解剖变化如何改善T2 DM的了解有限。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变化如何改善T2 DM的理解。基于我们建立的包含RYGB前后纵向组织样本的组织库，我们处于一个独特的位置，可以与PNNL合作并进行这些研究。此外，对RYGB患者治疗前后空腹血浆的初步蛋白质组学分析支持这一假设，并提供了概念证据。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，并有可能确定新的药物疗法。此外，我们预计他们将为未来的研究确定潜在的调解人，为未来的赠款提交生成初步数据，并为出版提供科学数据。

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.