项目名称: 探讨胰岛β细胞复分化在胃绕道手术后胰岛改善中的作用
项目编号: No.81471047
项目类型: 面上项目
立项/批准年度: 2015
项目学科: 医药、卫生
项目作者: 周华荣
作者单位: 中国科学院上海生命科学研究院
项目金额: 80万元
中文摘要: 在成熟个体中β细胞的来源存在干细胞分化和β细胞自我复制两种假说。最近研究表明,糖尿病个体中β细胞能够去分化为非β细胞(内分泌前体细胞)。我们前期的结果提示胃绕道手术后,胰岛明显改善,伴随去分化的胰岛β细胞减少,与转录因子FOXO-1显著相关。本课题通过谱系示踪胰岛β细胞和双向示踪去分化的胰岛β细胞,阐明在转基因小鼠2型糖尿病胃绕道手术后,去分化的胰岛β细胞在体内外能否复分化,同时揭示与FOXO-1相关的主要信号分子的变化。该研究不仅能进一步澄清成熟个体中β细胞的来源,同时能在不进行胰岛分离的情况下,获得活体胰岛β细胞多种状态的特异基因表达图谱,评价复分化细胞作为糖尿病β细胞替代治疗的可能性,为2型糖尿病治疗和改善胰岛失代偿提供新途径。
中文关键词: 2型糖尿病;胰岛β细胞
英文摘要: The source of β cells in adults has two hypotheses: differentiation of stem cells and β-cell self-replicating. Recent studies have shown that β cells can de-differentiate to a non-β cells (endocrine precursor cells)in diabetic individuals. Our preliminary results suggest that gastric bypass surgery has significantly improved islet structures and functions, along with decrement of the de-differentiation of islet β cells and increment of FOXO-1 expression. This application using islet β cell lineage tracing and bidirectional tracing of dedifferentiated islet β cells, set forth in the transgenic mice after gastric bypass surgery in type 2 diabetes: 1. Whether de-differentiated islet β cells can re-differentiate in vitro and in vivo? 2. Revealing the changes of FOXO-1-related major signaling molecules control the dramatic changes. This study will not only further clarify the source of β cells in adult individuals, but also can obtain the islet β cells specific gene expression profiles of various statusbe in vivo without separation islets, evaluation of re- differentiated β cells as a sourse of cell replacement therapy in diabetics, providing a new way for the treatment of type 2 diabetes.
英文关键词: type 2 diabetes;pancreatic beta cells