Overexpression of constitutive active form of ActRIB in pancreas beta cells leads to impaired insulin secretion in mice.
Overexpression of constitutive active form of ActRIB in pancreas beta cells leads to impaired insulin secretion in mice.
复制标题
ActRIB 组成型活性形式在胰腺 β 细胞中的过度表达会导致小鼠胰岛素分泌受损。
DOI：
10.1016/j.bbrc.2014.05.141
复制
发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Teramoto N
中科院分区：
文献类型：
--
作者：
Nomura M;Morinaga H;Hei-lay Z;Wang L;Hasuzawa N;Takayanagi R;Teramoto N
在基因消融小鼠的研究中，通过激活素IIB型受体（ActRIIB）和Smad 2的激活素信号传导已显示出不仅调节胰腺β细胞质量，而且调节胰岛素分泌。然而，仍然不清楚激活素信号传导功能的获得是否参与胰腺β细胞质量和胰岛素分泌的调节。为了鉴定激活素信号传导在胰腺辟田胞中的不同作用，使用Cre-loxP系统通过激活素IB型受体（ActRIB）激活胰腺辟田胞中的信号传导。所得小鼠（胰腺β细胞特异性ActRIB转基因（Tg）小鼠; ActRIBCAβTg）显示葡萄糖刺激的胰岛素分泌（GSIS）缺陷和葡萄糖耐量进行性损害。膜片钳技术显示突变体β细胞ATP敏感性钾通道（KATP channels）活性降低。这些结果表明，胰腺β细胞中GSIS可能需要适当水平的激活素信号传导，并且激活素信号传导涉及KATP通道活性的调节。
In studies of gene-ablated mice, activin signaling through activin type IIB receptors (ActRIIB) and Smad2 has been shown to regulate not only pancreatic β cell mass but also insulin secretion. However, it still remains unclear whether gain of function of activin signaling is involved in the modulation of pancreatic β cell mass and insulin secretion. To identify distinct roles of activin signaling in pancreatic β cells, the Cre-loxP system was used to activate signaling through activin type IB receptor (ActRIB) in pancreatic β cells. The resultant mice (pancreatic β cell-specific ActRIB transgenic (Tg) mice; ActRIBCAβTg) exhibited a defect in glucose-stimulated insulin secretion (GSIS) and a progressive impairment of glucose tolerance. Patch-clamp techniques revealed that the activity of ATP-sensitive K+channels (KATPchannels) was decreased in mutant β cells. These results indicate that an appropriate level of activin signaling may be required for GSIS in pancreatic β cells, and that activin signaling involves modulation of KATPchannel activity.