Enhanced expression of PDX-1 and Ngn3 by exendin-4 during β cell regeneration in STZ-treated mice
Enhanced expression of PDX-1 and Ngn3 by exendin-4 during β cell regeneration in STZ-treated mice
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DOI：
10.1016/j.bbrc.2004.12.120
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发表时间：
2005-02-25
影响因子：
3.1
通讯作者：
Araki, E
中科院分区：
文献类型：
--
作者：
Kodama, S;Toyonaga, T;Araki, E
胰腺祖细胞存在于成年胰腺中，在病理条件下转化为内分泌细胞。为了阐明P细胞再生的机制，用链脲佐菌素（STZ组）或链脲佐菌素和exendin-4（STZ + Ex-4组）处理小鼠，并研究PDX-1、Ngn 3、胰岛素、IRS-2和Foxo 1的表达。PDX-1 mRNA的双相上调和Ngn 3 mRNA的诱导发生后不久，PDX-1表达的第一次增加，在胚胎发生过程中观察到的模式相似。STZ组PDX-1阳性细胞仅出现在胰岛样细胞团（ICCs）中，而STZ + Ex-4组PDX-1阳性细胞既出现在导管中，也出现在ICCs中。Ngn 3阳性细胞出现在ICC中，但在导管中没有。因此，再生似乎主要发生在胰岛内干/祖细胞。Exendin-4上调PDX-1的表达，从而增加IRS-2的表达和Foxo 1从细胞核到细胞质的移位。对P细胞再生的进一步分析将有助于糖尿病新疗法的设计。(C)2004年爱思唯尔公司All rights reserved.
Progenitor cells exist in the adult pancreas and transform to endocrine cells in pathological conditions. To address the mechanism of P cell regeneration, mice were treated with streptozotocin (STZ group) or streptozotocin and exendin-4 (STZ + Ex-4 group), and the expression of PDX-1, Ngn3, insulin, IRS-2, and Foxo1 was investigated. PDX-1 mRNA was upregulated biphasically and induction of Ngn3 mRNA occurred shortly after the first increase of PDX-1 expression, a pattern similar to that observed during embryogenesis. PDX-1-positive cells appeared only in islet-like cell clusters (ICCs) in STZ group, but they appeared both in ducts and ICCs in STZ + Ex-4 group. Ngn3-positive cells emerged in ICCs but not in ducts. Therefore, regeneration seemed to occur mainly from intra-islet stem/progenitor cells. Exendin-4 upregulated PDX-1 expression which paralleled increased IRS-2 expression and translocation of Foxo1 from nucleus to cytoplasm. Further analysis of P cell regeneration should help in the design of novel therapy for diabetes. (C) 2004 Elsevier Inc. All rights reserved.