Neogenesis of β-cells in adult BETA2/NeuroD-deficient mice
Neogenesis of β-cells in adult BETA2/NeuroD-deficient mice
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DOI：
10.1210/mend.16.3.0784
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发表时间：
2002-03
影响因子：
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通讯作者：
Hsiang-Po Huang;K. Chu;E. Némoz-Gaillard;Dorit Elberg;M. Tsai
中科院分区：
文献类型：
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作者：
Hsiang-Po Huang;K. Chu;E. Némoz-Gaillard;Dorit Elberg;M. Tsai
BETA2/NeuroD是一种基本的螺旋-环-螺旋转录因子，在胰腺内分泌细胞发育过程中表达，调控胰岛素基因的表达。我们之前证明，BETA2/ neurod缺陷小鼠的内分泌胰腺会发生大量凋亡，因此，动物在出生后不久就死于糖尿病。本研究表明，在新的遗传背景下，有相当一部分β a2缺陷小鼠可以通过β细胞新生过程在糖尿病中存活并存活到成年。形态学检查表明，胰腺β-细胞质量恢复到与野生型动物相当的水平，而α-细胞质量未恢复。然而，新形成的胰岛细胞不能形成成熟的朗格汉斯胰岛，这表明BETA2在正常胰岛结构的形态发生中起着不可或缺的作用。此外，免疫组化检查显示，BETA2/ neurod缺陷小鼠新形成的β-细胞有两种来源：直接从胰管树出芽或从胰管树出芽。
BETA2/NeuroD, a basic helix-loop-helix transcription factor, is expressed in pancreatic endocrine cells during development and regulates insulin gene expression. We demonstrated previously that the endocrine pancreas of BETA2/NeuroD-deficient mice undergoes massive apoptosis and, consequently, animals die of diabetes shortly after birth. Here we show that a significant fraction of BETA2-deficient mice in a new genetic background can survive diabetes and live to adulthood through the process of β-cell neogenesis. Morphometric examination indicates that pancreatic β-, but not α-cell mass, was restored to a level comparable to that of wild-type animals. However, the newly formed islet cells cannot form mature islets of Langerhans, indicating an indispensable role of BETA2 in morphogenesis of normal islet structure. Furthermore, immunohistochemical examinations revealed that newly formed β-cells of BETA2/NeuroD-deficient mice come from two sources: either directly budding from the pancreatic ductal tree or fr...