Hypoplasia of endocrine and exocrine pancreas in homozygous transgenic TGF-β1
Hypoplasia of endocrine and exocrine pancreas in homozygous transgenic TGF-β1
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DOI：
10.1016/j.mce.2004.08.007
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发表时间：
2005-01-14
影响因子：
4.1
通讯作者：
Itakura, M
中科院分区：
文献类型：
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作者：
Moritani, M;Yamasaki, S;Itakura, M
我们通过胰高血糖素启动子产生了表达TGF-β 1活性形式的纯合转基因小鼠（纯合NOD-TGF-β 1）。NOD-TGF-β 1纯合子患者中84.6%为重度糖尿病，糖耐量异常。和低血清胰岛素水平内分泌和整个胰腺的最终大小减小。分别6%和34%。与野生型小鼠相比。与C57 BL/6（B6-TGF-β 1）的纯合N-2回交显示没有糖尿病。但葡萄糖耐量受损和血清胰岛素水平低。在纯合子NOD-TGF-β 1 t中，p15（INK 4 b）的表达在胰岛中比在野生型小鼠中诱导了3.4倍。基于这些，我们得出的结论是：首先，胰岛中过度的旁分泌TGF-β 1信号传导导致内分泌和外分泌胰腺发育不全，其次，TGF-β 1可能通过p15（INK 4 b）调节细胞周期来减少内分泌和外分泌胰腺的最终大小至少在内分泌胰腺中是这样。第三，胰岛TGF-β 1的发育不良作用与遗传背景无关。(C)2004爱思唯尔爱尔兰有限公司保留所有权利。
We generated the homozygous transgenic mice with expression of the active form of TGF-beta1 by the glucagon promoter (homozygous NOD-TGF-beta1). The homozygous NOD-TGF-beta1 showed severe diabetes in 84.6%, impaired glucose tolerance. and low-serum insulin levels. The final size of endocrine and whole pancreas decreased. respectively. to 6 and 34%. compared to wild-type mice. The homozygous N-2 backcross to C57BL/6 (B6-TGF-beta1) showed no diabetes. but impaired glucose tolerance and low serum insulin levels. In homozygous NOD-TGF-beta1 t, the expression of p15(INK4b) was induced by 3.4-fold in pancreatic islets than that in wild-type mice. Based on these, we conclude first that excessive paracrine TGF-beta1 signaling in islets results in endocrine and exocrine pancreatic hypoplasia, second that TGF-beta1 decrease the final size of endocrine and exocrine pancreas presumably through regulating cell cycle via p15(INK4b) at least in endocrine pancreas. and third that hypoplastic action of TGF-beta1 of pancreatic islets is independent of the genetic background. (C) 2004 Elsevier Ireland Ltd. All rights reserved.