YR 50 PROJ- ROBERTS PRIMATE ISLET

YR 50 项目 - 罗伯茨灵长类胰岛

• 批准号: 8173289
• 负责人: Charles T Roberts
• 金额: $ 4.76万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8173289
• 关键词: Address; Autoimmune Process; Behavior; Cardiovascular Diseases; Cell physiology; Cells; Computer Retrieval of Information on Scientific Projects Database; Culture Techniques; Defect; Diabetes Mellitus; Epidemic; Evaluation; Failure; Funding; Glucose; Grant; Human; Institution; Insulin; Insulin Resistance; Insulin-Dependent Diabetes Mellitus; Islet Cell; Maintenance; Mediating; Microgravity; Molecular; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Peripheral; Physiological; Prediabetes syndrome; Primates; Protocols documentation; Research; Research Personnel; Resources; Source; United States National Institutes of Health; diabetes mellitus therapy; insulin secretion; islet; nonhuman primate; novel; restoration

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. There is a worldwide epidemic of obesity, diabetes, and attendant serious complications, including cardiovascular disease. Type-1 diabetes mellitus (T1DM) is characterized by autoimmune-mediated ¿-cell destruction, while T2DM is characterized by progressive ¿-cell insufficiency. The transition from pre-diabetes to frank T2DM occurs when ¿-cell function becomes inadequate to maintain insulin levels high enough to overcome peripheral insulin resistance. Thus, ¿-cell failure is the critical defect in both T1 and T2DM. The successful treatment of T1DM and comprehensive therapy for T2DM will involve the propagation, maintenance, or restoration of ¿-cell/islet function, which requires an understanding of the requirements for the survival, function, and potential expansion of intact islets ex vivo. We hypothesize that novel culture techniques will increase ex vivo primate islet survival and function and amenability to molecular analyses. We will address this hypothesis through the following specific aims. 1. Determine the effects of physiological O2 and microgravity/3-D culture on islet survival, integrity, and function. 2. Assess the effect of current diabetes therapies on the function of isolated primate islets. 3. Assess potential factors stimulating ¿-cell replication. 4. Extrapolate non-human primate islet behavior to human islets. We have established successful protocols for islet isolation, assessment of islet viability, and glucose-stimulated insulin secretion. We are now initiating proposed studies on evaluation of various culture conditions on islet viability and function.

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。 肥胖症、糖尿病和伴随的严重并发症（包括心血管疾病）在世界范围内流行。 1型糖尿病（T1 DM）的特征是自身免疫介导的<$-细胞破坏，而T2 DM的特征是进行性<$-细胞不足。 当胰岛细胞功能不足以维持足够高的胰岛素水平以克服外周胰岛素抵抗时，就会发生从糖尿病前期到坦率的T2 DM的转变。 因此，细胞衰竭是T1和T2 DM的关键缺陷。 T1 DM的成功治疗和T2 DM的综合治疗将涉及到细胞/胰岛功能的增殖、维持或恢复，这需要了解完整胰岛离体存活、功能和潜在扩增的要求。 我们假设新的培养技术将增加离体灵长类动物胰岛的存活率和功能，以及对分子分析的适应性。 我们将通过以下具体目标来解决这一假设。 1. 确定生理O2和微重力/3-D培养对胰岛存活、完整性和功能的影响。 2. 评估目前糖尿病治疗对分离的灵长类动物胰岛功能的影响。 3. 评估刺激细胞复制的潜在因素。 4. 将非人类灵长类动物胰岛行为外推至人类胰岛。 我们已经建立了成功的协议胰岛分离，胰岛活力的评估，和葡萄糖刺激的胰岛素分泌。 我们现在正在开展关于评估各种培养条件对胰岛活力和功能的影响的研究。