Luo Xiao, Li Ting, Zhu Yue, Dai Yunbin, Zhao Jianwei, Guo Zhan-Yun, Wang Ming-Wei
*The National Center for Drug Screening and the Chinese Academy of Sciences Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Shanghai, China.
†Institute of Protein Research, College of Life Sciences and Technology, Tongji University, Shanghai, China.
Biochem J. 2015 Mar 15;466(3):467-73. doi: 10.1042/BJ20141113.
Insulin-like peptide 5 (INSL5), a member of the insulin/relaxin superfamily, can activate the G-protein-coupled receptor relaxin/insulin-like family peptide receptor 4 (RXFP4), but its precise biological functions are largely unknown. Recent studies suggest that INSL5/RXFP4 is involved in the control of food intake and glucose homoeostasis. We report in the present study that RXFP4 is present in the mouse insulinoma cell line MIN6 and INSL5 augments glucose-stimulated insulin secretion (GSIS) both in vitro and in vivo. RXFP4 is also expressed in the mouse intestinal L-cell line GLUTag and INSL5 is capable of potentiating glucose-dependent glucagon-like peptide-1 (GLP-1) secretion in GLUTag cells. We propose that the insulinotrophic effect of INSL5 is probably mediated through stimulation of insulin/GLP-1 secretion and the INSL5/RXFP4 system may be a potential therapeutic target for Type 2 diabetes.
胰岛素样肽5（INSL5）是胰岛素/松弛素超家族的成员，可激活G蛋白偶联受体松弛素/胰岛素样家族肽受体4（RXFP4），但其确切的生物学功能在很大程度上尚不清楚。最近的研究表明，INSL5/RXFP4参与食物摄入和葡萄糖稳态的调控。我们在本研究中报告，RXFP4存在于小鼠胰岛素瘤细胞系MIN6中，并且INSL5在体外和体内均可增强葡萄糖刺激的胰岛素分泌（GSIS）。RXFP4也在小鼠肠道L细胞系GLUTag中表达，并且INSL5能够增强GLUTag细胞中葡萄糖依赖性胰高血糖素样肽-1（GLP-1）的分泌。我们提出，INSL5的促胰岛素作用可能是通过刺激胰岛素/GLP-1分泌介导的，并且INSL5/RXFP4系统可能是2型糖尿病的一个潜在治疗靶点。
