Insulinotropic hormone glucagon-like peptide-1 differentiation of human pancreatic islet-derived progenitor cells into insulin-producing cells.
Insulinotropic hormone glucagon-like peptide-1 differentiation of human pancreatic islet-derived progenitor cells into insulin-producing cells.
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DOI：
10.1210/endo.143.8.8973
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发表时间：
2002-08
期刊：
影响因子：
4.8
通讯作者：
E. Abraham;C. Leech;Julia C. Lin;H. Zulewski;J. Habener
中科院分区：
文献类型：
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作者：
E. Abraham;C. Leech;Julia C. Lin;H. Zulewski;J. Habener
胰高血糖素样肽-1 （Glucagon-like peptide-1, GLP-1）是一种肠促胰岛素激素，来源于胰高血糖素原的加工过程，对产生胰岛素的胰岛β细胞发挥促胰岛素作用。最近，GLP-1被证明可以刺激β细胞的生长和分化（新生），其作用似乎是通过诱导同源结构域蛋白IDX-1（胰岛十二指肠同源盒1；也称为PDX-1，胰腺和十二指肠同源盒基因；IPF-1，胰岛素启动因子）的表达来实现的，这是胰腺发育和β细胞特异性基因表达所必需的。先前我们在胰岛和胰腺导管中发现了多潜能祖细胞，称为巢蛋白阳性胰岛源性祖细胞（NIPs）。在这里，我们报道了功能性GLP-1受体在NIPs上的表达，并且GLP-1刺激NIPs向胰岛素生成细胞的分化。此外，融合培养的NIP表达胰高血糖素原基因，分泌GLP-1。这些发现提示了一个胰岛发育模型，其中胰腺祖细胞表达GLP-1受体和胰高血糖素原，并形成GLP-1。局部产生的GLP-1可能作为NIPs上受体的自分泌/旁分泌发育形态因子，导致IDX-1的激活和胰岛素原基因的表达，从而产生β细胞表型。GLP-1可能是胰腺胚胎发育和成人胰岛β细胞新生的重要形态因子。
Glucagon-like peptide-1 (GLP-1) is an intestinal incretin hormone, derived from the processing of proglucagon, that exerts insulinotropic actions on insulin-producing pancreatic islet beta-cells. Recently GLP-1 was shown to stimulate the growth and differentiation (neogenesis) of beta-cells and appears to do so by inducing the expression of the homeodomain protein IDX-1 (islet duodenum homeobox-1; also known as PDX-1, pancreatic and duodenal homeobox gene; and as IPF-1, insulin promoter factor), which is required for pancreas development and the expression of beta-cell-specific genes. Earlier we identified multipotential progenitor cells in the islet and ducts of the pancreas, termed nestin-positive islet-derived progenitor cells (NIPs). Here we report the expression of functional GLP-1 receptors on NIPs and that GLP-1 stimulates the differentiation of NIPs into insulin-producing cells. Furthermore, confluent NIP cultures express the proglucagon gene and secrete GLP-1. These findings suggest a model of islet development in which pancreatic progenitor cells express both GLP-1 receptors and proglucagon with the formation of GLP-1. Locally produced GLP-1 may act as an autocrine/paracrine developmental morphogen on receptors on NIPs, resulting in the activation of IDX-1 and the expression of the proinsulin gene conferring a beta-cell phenotype. GLP-1 may be an important morphogen both for the embryonic development of the pancreas and for the neogenesis of beta-cells in the islets of the adult pancreas.