BETA CELL ADAPTATION TO STRESS IN BABOON PANCREAS AFTER PARTIAL PANCREATECTOMY

狒狒胰腺部分切除术后β细胞对应激的适应

• 批准号: 8357685
• 负责人: Franco Battista Ennio Folli
• 金额: $ 10.49万
• 依托单位: TEXAS BIOMEDICAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357685
• 关键词: Acute; Antidiabetic Drugs; B-Lymphocytes; Beta Cell; Blood Circulation; Cell physiology; Cells; Cellular Stress; Funding; Glucose; Grant; Human; Hyperglycemia; Insulin; Measures; National Center for Research Resources; Non-Insulin-Dependent Diabetes Mellitus; Operative Surgical Procedures; Pancreas; Pancreas Part; Pancreatectomy; Papio; Pharmaceutical Preparations; Pharmacological Treatment; Pharmacotherapy; Primates; Principal Investigator; Procedures; Production; Research; Research Infrastructure; Resources; Source; Stress; Testing; United States National Institutes of Health; cost; exenatide; improved; insulin secretion; response

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.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 本研究将使用狒狒。我们将通过切除部分胰腺来造成胰岛素分泌不足，这一手术称为部分胰腺切除术。我们打算证明胰腺手术后胰岛素的释放量减少，并且特定的药物治疗可能会保护胰岛素的产生和释放，即使在手术导致的b细胞应激（负责胰岛素产生的细胞）存在的情况下。被测试的药物被称为exenglutamine，一种被批准作为人类抗糖尿病药物治疗的药物。为了精确测量分泌的胰岛素量，我们将通过一种称为高血糖钳夹的程序来产生胰岛素分泌需求的急剧增加，在该程序中，我们通过静脉注射大量葡萄糖，以维持狒狒血流中固定的葡萄糖浓度，同时测量胰岛素产生的相应反应。我们希望观察部分胰腺切除术前后胰岛素水平的变化。我们还希望证明exenlavin改善部分胰腺切除术后的B细胞功能。这种类型的研究对于帮助开发2型糖尿病的潜在新疗法非常有价值。