GASTROINTESTINAL PEPTIDES IN GLUCOSE REGULATION

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。 最近的研究发现，几种胃肠道(GI)肽与2型糖尿病的发生有关。此外，操作胃肠肽可能被证明是治疗和预防这种疾病的有效手段。特别是，高血糖素样多肽-1(GLP-1)、葡萄糖依赖的促胰岛素多肽(GIP)、多肽YY(PYY)和Ghrelin的浓度调节已被证明在治疗啮齿动物模型中的葡萄糖耐量异常或2型糖尿病方面有效。此外，人类Roux-en Y胃旁路手术后2型糖尿病的显著缓解归因于这些多肽的变化。因此，这些观察结果表明，同时操作两个或更多这些胃肠肽可能为2型糖尿病提供新的治疗方式。因此，发展动物模型来研究胃旁路手术和胃肠肽对糖代谢的影响是糖尿病研究的首要任务。考虑到可以安全地获得大量血液，狒狒代表了这种模型的有力候选者。然而，更清楚地了解正常的狒狒GI肽生理学将是重要的第一步。目前西南国家灵长类中心的初步研究将确定10只成年雄性狒狒对肠道葡萄糖挑战的正常GLP-1、GIP、PYY和Ghrelin反应。假设在狒狒身上观察到的反应将与人类相似，即GLP-1、GIP和PYY浓度增加，Ghrelin浓度下降。这些数据将用于未来输注方案的设计，以评估这些多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将狒狒作为研究胃旁路手术引起的胃肠肽改变的模型的实用性。

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.