Mukai Eri, Toyoda Kentaro, Kimura Hiroyuki, Kawashima Hidekazu, Fujimoto Hiroyuki, Ueda Masashi, Temma Takashi, Hirao Konomu, Nagakawa Kenji, Saji Hideo, Inagaki Nobuya
Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan.
Biochem Biophys Res Commun. 2009 Nov 20;389(3):523-6. doi: 10.1016/j.bbrc.2009.09.014. Epub 2009 Sep 6.
We examined exendin(9-39), an antagonist of glucagon-like peptide-1 (GLP-1) receptor (GLP-1R), as a potential probe for imaging of pancreatic beta-cells. To evaluate in vitro receptor specificity, binding assay was performed using dispersed mouse islet cells. Binding assay showed competitive inhibition of [(125)I]BH-exendin(9-39) binding by non-radioactive exendin(9-39). To assess in vivo selectivity, the biodistribution was evaluated by intravenous administration of [(125)I]BH-exendin(9-39) to mice. Radioactivity of harvested pancreas reached highest levels at 60 and 120min among organs examined except lung. Pre-administration of excess non-radioactive exendin(9-39) remarkably and specifically blocked the radioactivity of pancreas. After [(125)I]BH-exendin(9-39) injection into transgenic mice with pancreatic beta-cells expressing GFP, fluorescent and radioactive signals of sections of pancreas were evaluated with an image analyzer. Imaging analysis showed that the fluorescent GFP signals and the radioactive signals were correspondingly located. Thus, the GLP-1R antagonist exendin(9-39) may serve as a useful probe for pancreatic beta-cell imaging.
我们研究了胰高血糖素样肽-1（GLP-1）受体（GLP-1R）拮抗剂艾塞那肽（9-39）作为胰腺β细胞成像潜在探针的可能性。为评估体外受体特异性，使用分散的小鼠胰岛细胞进行结合试验。结合试验显示非放射性艾塞那肽（9-39）对[（125）I]BH-艾塞那肽（9-39）的结合具有竞争性抑制作用。为评估体内选择性，通过向小鼠静脉注射[（125）I]BH-艾塞那肽（9-39）来评估生物分布。在所检查的器官中，除肺外，收获的胰腺放射性在60分钟和120分钟时达到最高水平。预先给予过量的非放射性艾塞那肽（9-39）可显著且特异性地阻断胰腺的放射性。向表达绿色荧光蛋白（GFP）的胰腺β细胞转基因小鼠注射[（125）I]BH-艾塞那肽（9-39）后，用图像分析仪评估胰腺切片的荧光和放射性信号。成像分析表明荧光GFP信号和放射性信号相应定位。因此，GLP-1R拮抗剂艾塞那肽（9-39）可能是一种用于胰腺β细胞成像的有用探针。
