胰高血糖素样肽1与干细胞定向分化

Glucagon-Like PeptideⅠand Targeted Differentiation of Stem Cells

糖尿病已经成为21世纪严重威胁人类健康的疾病之一。胰岛移植被认为是治疗Ⅰ型和部分Ⅱ型糖尿病的最有效方法。然而,供体组织来源的匮乏限制了其应用。随着细胞移植和组织工程的日益发展,干细胞研究为新型胰岛的来源开辟了新的途径。干细胞定向诱导分化的关键是筛选合适的诱导剂以及优化诱导微环境,使干细胞培养微环境尽可能接近体内正常细胞发育分化的微环境,从而有利于干细胞适宜生长及定向分化。最近研究证实,胰高血糖素样肽1(Glucagon-Like PeptideⅠ,GLP-1)在干细胞向胰岛样细胞诱导分化中具有显著作用。因此,为了更好地应用GLP-1在干细胞定向分化中的潜能、促进应用干细胞治疗糖尿病新疗法研究的进程及干细胞定向分化技术逐渐成熟,就胰高血糖素样肽-1及它诱导干细胞定向分化胰岛样细胞的研究进展作一阐述。

Diabetes mellitus has become one of the diseases which threaten the heath of human being in the 21st century. A goal of research in diabetes is to find a way to increase the number of functional insulin-producing cells. Islet transplantation has been considered to be the most effective approach to cure type Ⅰ and part of type Ⅱ diabetes mellitus. This approach, however, is severely limited by an inadequate supply of donor islets available for transplantation. Moreover, recent progress of stem cells research has shown that stem cells may act as a new source of islet transplantation in diabetes mellitus treatment. Recent evidence indicates that Glucagun-Like Peptide Ⅰ （ GLP-1 ） plays a very important role in targeted differentiation of stem cells into Insulin-Producing Cells and pancreatic development. GLP-1 is an intestine-derived insulinotropic hormone that stimulates glucose dependent insulin production and secretion. GLP-1 can induce differentiation of stem cells into insulin-producing cells, which is achieved by up regulation of PDX-1 expression. PDX-1 is a transcription factor critical for pancreatic development and endocrine cell neogenesis and a marker for pancreatic stem cells. These new findings suggest an approach to create Insulin-Producing cells in vitro by expanding stem/progenitor cells and then to convert them into Insulin-Producing cells by treatment with GLP-1. Thus GLP-1 may be a means by which to create Insulin-Producing cells ex vivo for transplantation into patients with insulinopenic type Ⅰ diabetes and severe forms of type Ⅱ diabetes. This article reviews recent progress about GLP-1 and targeted differentiation of stem cells induced by GLP-1.