GASTROINTESTINAL PEPTIDES IN GLUCOSE REGULATION

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 最近的研究结果表明，几种胃肠道（GI）肽与2型糖尿病的发生有关。 此外，GI肽的操作可能被证明是治疗和预防该疾病的有效手段。 特别地，胰高血糖素样肽-I（GLP-1）、葡萄糖依赖性促胰岛素多肽（GIP）、肽YY（PYY）和生长素释放肽浓度的调节已显示在治疗啮齿动物模型中的葡萄糖耐受不良或2型糖尿病中有效。 此外，人类Roux-en Y胃旁路手术后2型糖尿病的显著消退归因于这些肽的改变。 因此，这些观察结果表明，同时操作两种或更多种这些GI肽可以为2型糖尿病提供新的治疗方式。 因此，开发动物模型来研究胃旁路手术和GI肽对葡萄糖代谢的影响是糖尿病研究中的一个高度优先事项。 鉴于可以安全达到的大量血液，狒狒是这种模型的有力候选者。 然而，更清楚地了解正常狒狒胃肠道肽生理学将是重要的第一步。目前的西南国家灵长类动物中心试点研究将确定正常GLP-1，GIP，PYY，和胃饥饿素的反应，肠道葡萄糖的挑战，在10个成年雄性狒狒。 假设在狒狒中观察到的反应与人类相似，即GLP-1、GIP和PYY浓度升高，胃饥饿素浓度降低。 这些数据将用于设计未来的输注方案，以评估这些肽对葡萄糖代谢的协同或拮抗作用。 此外，这些数据将有助于确定狒狒作为研究胃旁路手术引起的GI肽改变的影响的模型的实用性。

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. Recent research findings have implicated several gastrointestinal (GI) peptides in the development of type 2 diabetes. In addition, manipulation of GI peptides may prove to be an effective means of treating and preventing the disorder. In particular, the modulation of glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), peptide YY (PYY), and ghrelin concentrations have been shown to be effective in treating glucose intolerance or type 2 diabetes in rodent models. Moreover, the striking resolution of type 2 diabetes following roux-en Y gastric bypass surgery in humans has been attributed to the alterations in these peptides. Thus, these observations suggest that simultaneous manipulation of two or more of these GI peptides may provide new treatment modalities for type 2 diabetes. Hence, the development of animal models to study the effects of gastric bypass surgery and GI peptides on glucose metabolism is a high priority in diabetes research. Given, the large blood volumes that can be safely attained, the baboon represents a strong candidate for such a model. However, a clearer understanding of normal baboon GI peptide physiology will be an important initial step. The current Southwest National Primate Center pilot study will determine normal GLP-1, GIP, PYY, and ghrelin responses to an intestinal glucose challenge in ten adult male baboons. It is hypothesized that the responses observed in baboons will be similar to those of humans, i.e. increases in GLP-1, GIP, and PYY concentrations and a decrease in ghrelin concentrations. These data will be used in the design of future infusion protocols to assess the synergistic or antagonistic effects of these peptides on glucose metabolism. In addition, these data will help to determine the utility of the baboon as a model for studying the effects of GI peptide alteration resulting from gastric bypass surgery.