Dissecting the role of glucocorticoids on pancreas development
Dissecting the role of glucocorticoids on pancreas development
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DOI：
10.2337/diabetes.53.9.2322
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发表时间：
2004-09-01
期刊：
影响因子：
7.7
通讯作者：
Breant, B
中科院分区：
文献类型：
--
作者：
Gesina, E;Tronche, F;Breant, B
为了确定糖皮质激素是否参与胰腺发育，将体外大鼠胰腺芽的糖皮质激素治疗与特定胰腺细胞中缺乏糖皮质激素受体（GR）的转基因小鼠的分析相结合。在体外处理胚胎胰腺与地塞米松，糖皮质激素激动剂，诱导胰岛素表达细胞的数量减少和腺泡细胞面积增加一倍，表明糖皮质激素有利于腺泡分化，与此一致，表达的Pdx-1，Pax-6，Nkx6.1下调，而Ptf 1-p48和Hes-1的mRNA水平增加。小鼠中表达胰岛素的β细胞中GR基因的选择性失活（使用RIP-Cre转基因）对β细胞或α细胞质量没有可测量的后果，而Pdx-1（Pdx-Cre转基因）表达结构域中GR的缺失导致β细胞质量增加两倍，胰岛数量和大小增加，但成人中α细胞质量正常。这些结果表明，糖皮质激素在胰腺β细胞谱系中起重要作用，在激素基因表达开始之前起作用，并且还可能调节内分泌和外分泌细胞分化之间的平衡。
To determine whether glucocorticoids are involved in pancreas development, glucocorticoid treatment of rat pancreatic buds in vitro was combined with the analysis of transgenic mice lacking the glucocorticoid receptor (GR) in specific pancreatic cells. In vitro treatment of embryonic pancreata with dexamethasone, a glucocorticoid agonist, induced a decrease of insulin-expressing cell numbers and a doubling of acinar cell area, indicating that glucocorticoids favored acinar differentiation; in line with this, expression of Pdx-1, Pax-6, and Nkx6.1 was downregulated, whereas the mRNA levels of Ptf1-p48 and Hes-1 were increased. The selective inactivation of the GR gene in insulin-expressing beta-cells in mice (using a RIP-Cre transgene) had no measurable consequences on beta- or alpha-cell mass, whereas the absence of GR in the expression domain of Pdx-1 (Pdx-Cre transgene) led to a twofold increased beta-cell mass, with increased islet numbers and size but normal alpha-cell mass in adults. These results demonstrate that glucocorticoids play an important role in pancreatic beta-cell lineage, acting before hormone gene expression onset and possibly also modulating the balance between endocrine and exocrine cell differentiation.