Rong Guo Xing, Li Wang Xiao, Chen Yun, Hong Yuan Ya, Mei Chen Yong, Ding Yan, Fang Juan, Jiao Bian Liu, Sheng Li Dong
Hubei Key Laboratory of Embryonic Stem Cell Research, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, China.
Hubei Key Laboratory of Embryonic Stem Cell Research, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, China; Institute of Genomic Medicine, Wenzhou Medical University, Wenzhou, China.
Exp Cell Res. 2016 Jul 15;345(2):158-67. doi: 10.1016/j.yexcr.2015.09.012. Epub 2015 Sep 24.
Angiopoietin-like protein 8 (ANGPTL8)/betatrophin, a newly identified protein, is primarily expressed in the liver and regulates the glucose metabolic transition during fasting and re-feeding in mice with or without insulin resistance. These findings strongly suggest that ANGPTL8/betatrophin could be a novel glucose-lowering candidate medicine for type 2 diabetes. However, the molecular mechanisms by which ANGPTL8/betatrophin regulates glucose metabolism are poorly understood in human. Two sub-clones of HepG2 cells, ANGPTL8/betatrophin knockouts and ANGPTL8/betatrophin over-expressors, were established using TALENs (transcription activator-like effector nucleases) and through stable transfection, respectively. Over-expression of ANGPTL8/betatrophin enhanced the insulin-stimulated activation of the Akt-GSK3β or Akt-FoxO1 pathway, no matter whether the cells were present with insulin resistance or not. In contrast, knockout of ANGPTL8/betatrophin did not affect the Akt-GSK3β or Akt-FoxO1 pathway unless the HepG2 cells were preset with insulin resistance. Our results suggest that ANGPTL8/betatrophin might play an important role in glucose metabolism in the context of insulin resistance.
血管生成素样蛋白8（ANGPTL8）/β-促胰岛素分泌素是一种新发现的蛋白质，主要在肝脏中表达，并在有或无胰岛素抵抗的小鼠禁食和重新进食期间调节葡萄糖代谢转变。这些发现有力地表明，ANGPTL8/β-促胰岛素分泌素可能是一种用于2型糖尿病的新型降糖候选药物。然而，在人类中，ANGPTL8/β-促胰岛素分泌素调节葡萄糖代谢的分子机制尚不清楚。分别使用转录激活样效应核酸酶（TALENs）并通过稳定转染建立了HepG2细胞的两个亚克隆，即ANGPTL8/β-促胰岛素分泌素敲除细胞和ANGPTL8/β-促胰岛素分泌素过表达细胞。无论细胞是否存在胰岛素抵抗，ANGPTL8/β-促胰岛素分泌素的过表达都会增强胰岛素刺激的Akt-GSK3β或Akt-FoxO1信号通路的激活。相反，除非HepG2细胞预先存在胰岛素抵抗，否则敲除ANGPTL8/β-促胰岛素分泌素不会影响Akt-GSK3β或Akt-FoxO1信号通路。我们的结果表明，在胰岛素抵抗的情况下，ANGPTL8/β-促胰岛素分泌素可能在葡萄糖代谢中起重要作用。
