ANGPTL8/betatrophin alleviates insulin resistance via the Akt-GSK3β or Akt-FoxO1 pathway in HepG2 cells

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• 作者：Xing Rong Guo^a ; Xiao Li Wang^a ; Yun Chen^a ; ^e ; Ya Hong Yuan^a ; Yong Mei Chen^c ; Yan Ding^a ; Juan Fang^d ; Liu Jiao Bian^b ; ^{bianliujiao@sohu.com" class="auth_mail" title="E-mail the corresponding author} ; Dong Sheng Li^a ; ^{dsli1698@126.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：ANGPTL8/betatrophin ; Akt ; GSK3β ; FoxO1 ; Insulin resistance ; HepG2 cells
• 刊名：Experimental Cell Research
• 出版年：2016
• 出版时间：15 July 2016
• 年：2016
• 卷：345
• 期：2
• 页码：158-167
• 全文大小：8248 K

文摘

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.