Kyohara Mayu, Takayanagi Rie, Tsuno Takahiro, Ong Yajima Esther, Inoue Ryota, Yamashita Naoya, Okuyama Tomoko, Nishiyama Kuniyuki, Matsunaga Kohichi, Ishida Emi, Ito Shuichi, Terauchi Yasuo, Goshima Yoshio, Shirakawa Jun
Department of Endocrinology and Metabolism, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
Laboratory of Diabetes and Metabolic Disorders, Institute for Molecular and Cellular Regulation (IMCR), Gunma University, Maebashi, Japan.
Sci Rep. 2025 Mar 27;15(1):10546. doi: 10.1038/s41598-025-95300-7.
Semaphorins were initially identified as axon guidance molecules that were widely expressed and involved in divergent functions in various organs, including neuronal development and immunological processes. Collapsin response mediator proteins (CRMPs) are involved in the intracellular signaling of semaphorin 3A (Sema3a) and are highly expressed in the nervous system. However, the participation of semaphorins or their receptors plexins and CRMPs in the regulation of islet function remains unknown. In this study, we measured the expression of semaphorin, plexin, and CRMP families in mouse islets, and their expression levels were altered by treatment with high glucose or a glucokinase activator (GKA). The expression and phosphorylation of CRMP-2 in islets were upregulated in high-fat diet (HF)-fed obese mice, and the expression of CRMP-2 was downregulated in islets from db/db mice. HF-fed CRMP-2 knockout mice exhibited impaired glucose tolerance. These results indicated that the semaphorin/plexin/CRMP families in mouse islets might be involved in glucose metabolism partly through glucose/glucokinase.
信号素最初被鉴定为轴突导向分子，广泛表达并参与包括神经元发育和免疫过程在内的各种器官的不同功能。塌陷反应介导蛋白（CRMPs）参与信号素3A（Sema3a）的细胞内信号传导，在神经系统中高度表达。然而，信号素或其受体丛状蛋白和CRMPs在胰岛功能调节中的参与情况仍不清楚。在本研究中，我们测量了小鼠胰岛中信号素、丛状蛋白和CRMP家族的表达，并且它们的表达水平在高糖或葡萄糖激酶激活剂（GKA）处理后发生了改变。高脂饮食（HF）喂养的肥胖小鼠胰岛中CRMP-2的表达和磷酸化上调，而db/db小鼠胰岛中CRMP-2的表达下调。HF喂养的CRMP-2基因敲除小鼠表现出葡萄糖耐量受损。这些结果表明，小鼠胰岛中的信号素/丛状蛋白/CRMP家族可能部分通过葡萄糖/葡萄糖激酶参与葡萄糖代谢。
