Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi Ward, Fukuoka 812-8582, Japan.
Department of Pharmacology, Faculty of Medicine, Saga 849-8501, Japan.
Biochem Biophys Res Commun. 2014 Jul 18;450(1):440-6. doi: 10.1016/j.bbrc.2014.05.141. Epub 2014 Jun 10.
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 (KATP channels) 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 KATP channel activity.
在基因敲除小鼠的研究中，激活素通过激活素 IIB 型受体（ActRIIB）和 Smad2 的信号传导已被证明不仅可以调节胰岛β细胞的数量，还可以调节胰岛素的分泌。然而，目前仍不清楚激活素信号的功能获得是否参与了胰岛β细胞数量和胰岛素分泌的调节。为了确定激活素信号在胰岛β细胞中的不同作用，使用 Cre-loxP 系统在胰岛β细胞中激活激活素 I 型受体（ActRIB）的信号传导。由此产生的小鼠（胰岛β细胞特异性 ActRIB 转基因（Tg）小鼠；ActRIBCAβTg）表现出葡萄糖刺激的胰岛素分泌（GSIS）缺陷和葡萄糖耐量逐渐受损。膜片钳技术显示突变β细胞中 ATP 敏感性 K+通道（KATP 通道）的活性降低。这些结果表明，适当水平的激活素信号可能是胰岛β细胞中 GSIS 所必需的，并且激活素信号涉及 KATP 通道活性的调节。
