Department of Endocrinology and Metabolism, Kanazawa University Graduate School of Medical Sciences, Ishikawa 920-8641, Japan.
Endocr J. 2019 Aug 29;66(8):659-662. doi: 10.1507/endocrj.EJ19-0255. Epub 2019 Jul 31.
Many researchers pay attention to novel secretory factors, such as adipokines or osteokines, secreted by the tissues that were not formerly recognized as classical endocrine organs. The liver also contributes to the onset of various kinds of pathologies of type 2 diabetes and obesity by producing and releasing secretory proteins "hepatokines." By using the information of gene expression in human livers, we rediscovered selenoprotein P (SeP) and leukocyte cell-derived chemotaxin 2 (LECT2) as hepatokines involved in the onset of glucose intolerance. SeP was previously recognized as a selenium transport protein, but we revealed that SeP causes insulin resistance in the muscle and liver. SeP also reduces VEGF signal transduction in vascular endothelial cells, contributing the impaired angiogenesis in diabetes. Importantly, SeP impairs health-promoting effects of exercise training by suppressing reactive oxygen species (ROS)/adenosine monophosphate-dependent protein kinase (AMPK) pathway in the skeletal muscle through its receptor low-density lipoprotein receptor-related protein 1 (LRP1). LECT2, previously-reported as a neutrophil chemotactic protein, promotes skeletal muscle insulin resistance in obesity. Further studies are necessary to develop new diagnostic or therapeutic procedures targeting hepatokines to combat type 2 diabetes or obesity.
许多研究人员关注新型分泌因子，如脂肪因子或骨因子，这些因子由以前不被认为是经典内分泌器官的组织分泌。肝脏也通过产生和释放分泌蛋白“肝因子”，导致 2 型糖尿病和肥胖症的各种病理的发生。通过使用人类肝脏中的基因表达信息，我们重新发现了硒蛋白 P（SeP）和白细胞细胞衍生趋化因子 2（LECT2）作为与葡萄糖耐量异常相关的肝因子。SeP 以前被认为是一种硒转运蛋白，但我们发现 SeP 会导致肌肉和肝脏胰岛素抵抗。SeP 还通过其受体低密度脂蛋白受体相关蛋白 1（LRP1）降低血管内皮细胞中的 VEGF 信号转导，导致糖尿病中的血管生成受损。重要的是，SeP 通过其受体低密度脂蛋白受体相关蛋白 1（LRP1）抑制骨骼肌中的活性氧（ROS）/腺苷单磷酸依赖蛋白激酶（AMPK）途径，从而抑制运动训练的健康促进作用。LECT2，以前被报道为一种嗜中性粒细胞趋化蛋白，在肥胖症中促进骨骼肌胰岛素抵抗。需要进一步的研究来开发针对肝因子的新的诊断或治疗方法，以对抗 2 型糖尿病或肥胖症。
