• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Molecular and Cellular Biology >GTPase ARFRP1 Is Essential for Normal Hepatic Glycogen Storage and Insulin-Like Growth Factor 1 Secretion
【24h】

GTPase ARFRP1 Is Essential for Normal Hepatic Glycogen Storage and Insulin-Like Growth Factor 1 Secretion

机译：GTPase ARFRP1是正常肝糖原存储和胰岛素样生长因子1分泌必不可少的

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The GTPase ADP-ribosylation factor-related protein 1 (ARFRP1) is located at the trans-Golgi compartment and regulates the recruitment of Arf-like 1 (ARL1) and its effector golgin-245 to this compartment. Here, we show that liver-specific knockout of Arfrp1 in the mouse (Arfrp1liv?/?) resulted in early growth retardation, which was associated with reduced hepatic insulin-like growth factor 1 (IGF1) secretion. Accordingly, suppression of Arfrp1 in primary hepatocytes resulted in a significant reduction of IGF1 release. However, the hepatic secretion of IGF-binding protein 2 (IGFBP2) was not affected in the absence of ARFRP1. In addition, Arfrp1liv?/? mice exhibited decreased glucose transport into the liver, leading to a 50% reduction of glycogen stores as well as a marked retardation of glycogen storage after fasting and refeeding. These abnormalities in glucose metabolism were attributable to reduced protein levels and intracellular retention of the glucose transporter GLUT2 in Arfrp1liv?/? livers. As a consequence of impaired glucose uptake into the liver, the expression levels of carbohydrate response element binding protein (ChREBP), a transcription factor regulated by glucose concentration, and its target genes (glucokinase and pyruvate kinase) were markedly reduced. Our data indicate that ARFRP1 in the liver is involved in the regulation of IGF1 secretion and GLUT2 sorting and is thereby essential for normal growth and glycogen storage.
机译：GTPase ADP-核糖基化因子相关蛋白1（ARFRP1）位于 trans -Golgi隔室，并调节Arf-like 1（ARL1）及其效应物golgin-245募集到该隔室。在这里，我们显示小鼠中 Arfrp1 的肝脏特异性敲除（ Arfrp1 liv？/？）导致早期生长迟缓，这是与减少的肝胰岛素样生长因子1（IGF1）分泌有关。因此，抑制 Arfrp1 在原代肝细胞中导致IGF1释放的显着减少。但是，在不存在ARFRP1的情况下，IGF结合蛋白2（IGFBP2）的肝分泌不受影响。此外， Arfrp1 liv？/？小鼠的葡萄糖向肝脏转运减少，导致糖原存储减少了50％，并且糖原存储明显延迟。禁食和再喂食。葡萄糖代谢异常归因于 Arfrp1 liv？/？sup>肝脏中蛋白质水平的降低和葡萄糖转运蛋白GLUT2的细胞内滞留。由于葡萄糖摄入肝脏受损，碳水化合物反应元件结合蛋白（ChREBP），受葡萄糖浓度调节的转录因子及其靶基因（葡萄糖激酶和丙酮酸激酶）的表达水平明显降低。我们的数据表明肝脏中的ARFRP1参与了IGF1分泌和GLUT2分选的调节，因此对于正常生长和糖原存储至关重要。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号