Beta Cell Regeneration in Adult Pancreatic Islets

成人胰岛的β细胞再生

• 批准号: 6955912
• 负责人: GLADYS N. TEITELMAN
• 金额: $ 23.1万
• 依托单位: SUNY DOWNSTATE MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-18 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6955912
• 关键词: acinar cell; cell biology; cell differentiation; genetically modified animals; glucagon; hormone therapy; insulin; insulin dependent diabetes mellitus; laboratory mouse; mature animal; pancreatic islets; regeneration; stem cells; streptozotocin

DESCRIPTION (provided by applicant): Destruction of the insulin-producing beta cells leads to IDDM. The present goal of our work is to ascertain whether islets of adults contain beta precursor cells and to later establish protocols that will promote beta cell neogenesis. We developed a novel system in which new beta cells (NBC's) are induced to differentiate from putative beta cell precursors. Following depletion of existing beta cells by streptozotocin (SZ), a specific beta cell toxin, we found that cells expressing the phenotype characteristic of embryonic beta cells differentiated in islets and that this step was followed by the appearance of NBC's. Moreover, the restoration of normoglycemia by insulin therapy dramatically increased beta cell neogenesis. We now propose to identify the source of the NBC's. In specific aim #1, we will test whether IN+ cells that reappear in islets of SZ-treated mice following restoration of normoglycemia are NBC's or "old" beta cells that survived the effect of the toxin. To do this, we will test whether beta cell neogenesis occurs in mice in which "old" beta cells are identified by the presence of a molecular marker. In the specific aim #2, we will seek to determine whether the NBC's are generated by non-beta cells of the pancreas. To accomplish this goal, we will examine the process of beta cell neogenesis following SZ and insulin treatment in normoglycemic mice in which glucagon and amylase cells and the cells they generate are permanently labeled. These approaches could lend proof to the hypothesis that intra-islet precursors play an important role in beta cell regeneration in vivo in this and other models of IDDM.

描述（由申请人提供）：产生胰岛素的β细胞的破坏导致IDDM。我们工作的目前目标是确定成年人的胰岛是否包含β前体细胞，然后建立将促进β细胞新生成的方案。我们开发了一个新的系统，其中诱导新的β细胞（NBC）与假定的β细胞前体区分开。在特定的β细胞毒素（一种特定的β细胞毒素）中耗尽现有β细胞后，我们发现表达在胰岛中分化的胚胎β细胞的表型特征的细胞，此步骤之后是NBC的出现。此外，通过胰岛素治疗恢复正常血糖疗法大大增加了β细胞的新生成。现在，我们建议确定NBC的来源。在特定的目标＃1中，我们将测试在恢复正常血糖后，在SZ处理的小鼠胰岛中重新出现的+细胞中是否是NBC的NBC或“旧”β细胞，它们在毒素的作用中幸存下来。为此，我们将测试是否在通过分子标记的存在鉴定出“旧”β细胞的小鼠中发生β细胞新生成。在特定的目标＃2中，我们将寻求确定NBC是否是由胰腺非β细胞产生的。为了实现这一目标，我们将检查在SZ和胰岛素治疗后的β细胞新作用过程中，其中胰高血糖素和淀粉酶细胞及其产生的细胞被永久标记。这些方法可以证明以下假设：在IDDM和其他模型中，在体内和其他模型中，ISLEL内前体的前体在beta细胞再生中起着重要作用。