Shi Xiaoliu, Hu Xiao, Fang Xinlei, Jia Liangjie, Wei Fangchao, Peng Ying, Liu Menghao, Gao Aibo, Zhao Ke, Chen Fengyi, Hu Xiaoli, Hong Jie, Ning Guang, Song Yongfeng, Wang Jiqiu, Wang Yiguo
State Key Laboratory of Membrane Biology, MOE Key Laboratory of Bioinformatics, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China.
Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Nat Metab. 2025 Jan;7(1):68-83. doi: 10.1038/s42255-024-01175-9. Epub 2025 Jan 2.
Maintaining blood glucose homeostasis during fasting and feeding is crucial for the prevention of dysregulation that can lead to either hypo- or hyperglycaemia. Here we identified feimin, encoded by a gene with a previously unknown function (B230219D22Rik in mice, C5orf24 in humans), as a key modulator of glucose homeostasis. Feimin is secreted from skeletal muscle during feeding and binds to its receptor, receptor protein tyrosine kinase Mer (MERTK), promoting glucose uptake and inhibiting glucose production by activation of AKT. Administration of feimin and insulin synergistically improves blood glucose homeostasis in both normal and diabetic mice. Notably, a specific single nucleotide polymorphism (rs7604639, G>A) within the MERTK gene, causing an amino acid substitution (R466K) within the feimin-MERTK binding region, leads to reduced association with feimin and elevated postprandial blood glucose and insulin levels in humans. Our findings underscore a role of the feimin-MERTK signalling axis in glucose homeostasis, providing valuable insights into potential therapeutic avenues for diabetes.
在禁食和进食期间维持血糖稳态对于预防可能导致低血糖或高血糖的调节异常至关重要。在此，我们确定了由一个功能先前未知的基因（小鼠中的B230219D22Rik，人类中的C5orf24）编码的费明（feimin）是葡萄糖稳态的关键调节因子。费明在进食期间从骨骼肌分泌，并与其受体受体蛋白酪氨酸激酶Mer（MERTK）结合，通过激活AKT促进葡萄糖摄取并抑制葡萄糖生成。在正常小鼠和糖尿病小鼠中，给予费明和胰岛素可协同改善血糖稳态。值得注意的是，MERTK基因内的一个特定单核苷酸多态性（rs7604639，G>A），导致费明-MERTK结合区域内的氨基酸替换（R466K），会导致人类与费明的结合减少以及餐后血糖和胰岛素水平升高。我们的研究结果强调了费明-MERTK信号轴在葡萄糖稳态中的作用，为糖尿病的潜在治疗途径提供了有价值的见解。
