BETA CELL ADAPTATION TO STRESS IN BABOON PANCREAS AFTER PARTIAL PANCREATECTOMY

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。 这项研究将利用狒狒。我们将通过切除部分胰腺来造成胰岛素分泌不足，这一过程被称为部分胰腺切除术。我们打算证明这样的胰腺手术后胰岛素的释放量减少了，而且特定的药物治疗可能会保存胰岛素的产生和释放，即使在这种手术导致的b细胞应激(负责胰岛素产生的细胞)的情况下也是如此。被测试的药物被称为艾塞那肽，这是一种被批准用于人类的抗糖尿病药物。为了精确测量胰岛素的分泌量，我们将通过一种名为高血糖钳的程序来创造胰岛素分泌需求的急剧增加，在这种程序中，我们通过静脉注射大量葡萄糖，以便在测量胰岛素产生的相应反应的同时，保持狒狒血液中固定的葡萄糖浓度。我们期望观察胰腺部分切除术前后胰岛素水平的变化。我们还希望证明埃塞那肽能改善胰腺部分切除术后的B细胞功能。这种类型的研究对于帮助开发潜在的2型糖尿病新疗法非常有价值。

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. This study will utilize baboons. We will create a deficiency in insulin secretion by removing part of the pancreas, a procedure called a partial pancreatectomy. We intend to prove that the amount of insulin released is decreased after such pancreatic surgery, and that specific pharmacological treatments might preserve insulin production and release, even in the presence of b-cell stress (the cells responsible for insulin production) resulting from such surgery. The drug to be tested is called exenatide, a medication approved as an antidiabetic pharmacotherapy in humans. In order to precisely measure the amount of insulin secreted, we will create an acute increase in insulin secretory demand by a procedure called a hyperglycemic clamp, where we administer a large amount of glucose intravenously in order to maintain a fixed glucose concentration in the bloodstream of the baboons while measuring the corresponding response in insulin production. We expect to observe changes in insulin levels before and after the partial pancreatectomy. We also hope to demonstrate that exenatide improves B-cell function after partial pancreatectomy. This type of research is extremely valuable for helping to develop potential new treatments for type 2 diabetes.