GASTROINTESTINAL PEPTIDES IN GLUCOSE REGULATION

胃肠肽在血糖调节中的作用

• 批准号: 7716149
• 负责人: Anthony G. Comuzzie
• 金额: $ 0.25万
• 依托单位: TEXAS BIOMEDICAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7716149
• 关键词: Adult; Animal Model; Blood Volume; Computer Retrieval of Information on Scientific Projects Database; Data; Development; Diabetes Mellitus; Disease; Employee Strikes; Funding; Future; Glucose; Glucose Intolerance; Grant; Human; Infusion procedures; Institution; Intestines; Modality; Modeling; Non-Insulin-Dependent Diabetes Mellitus; Papio; Peptide YY; Peptides; Physiology; Pilot Projects; Primates; Protocols documentation; Research; Research Personnel; Resolution; Resources; Rodent Model; Source; Study models; United States National Institutes of Health; bariatric surgery; blood glucose regulation; design; gastric inhibitory polypeptide receptor; gastrointestinal; ghrelin; glucagon-like peptide 1; glucose metabolism; male; prevent; response

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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 最近的研究结果表明多种胃肠道 (GI) 肽与 2 型糖尿病的发生有关。 此外，胃肠道肽的操作可能被证明是治疗和预防该疾病的有效手段。 特别是，调节胰高血糖素样肽-1 (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已被证明可有效治疗啮齿动物模型中的葡萄糖不耐症或 2 型糖尿病。 此外，人类 roux-en Y 胃绕道手术后 2 型糖尿病的惊人缓解归因于这些肽的改变。 因此，这些观察结果表明，同时操作这些 GI 肽中的两种或多种可能为 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绕道手术和胃肠肽对葡萄糖代谢的影响是糖尿病研究的重中之重。 鉴于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，更清楚地了解正常狒狒胃肠道肽的生理学将是重要的第一步。目前西南国家灵长类动物中心的试点研究将确定 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。 据推测，在狒狒中观察到的反应与人类相似，即 GLP-1、GIP 和 PYY 浓度增加，而 ghrelin 浓度减少。 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绕道手术引起的胃肠肽改变影响的模型的效用。