title: ANGPTL8/betatrophin alleviates insulin resistance via the Akt-GSK3β or Akt-FoxO1 pathway in HepG2 cells.
abstract: 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.
authors.affiliation: Hubei Key Laboratory of Embryonic Stem Cell Research, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Rong Guo
authors.affiliation: Hubei Key Laboratory of Embryonic Stem Cell Research, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Li Wang
authors.affiliation: 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.
authors.forename: Yun
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Hubei Key Laboratory of Embryonic Stem Cell Research, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Hong Yuan
authors.affiliation: Clinical Laboratory, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Mei Chen
authors.affiliation: Hubei Key Laboratory of Embryonic Stem Cell Research, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Pathology, Academic College, Hubei University of Medicine, Shiyan, Hubei 442000, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Fang
authors.affiliation: College of Life Sciences, Northwest University, Xi'an, Shanxi 710069, China. Electronic address: bianliujiao@sohu.com.
authors.forename: Liu
authors.initials: L
authors.lastname: Jiao Bian
authors.affiliation: Hubei Key Laboratory of Embryonic Stem Cell Research, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, China. Electronic address: dsli1698@126.com.
authors.forename: Dong
authors.initials: D
authors.lastname: Sheng Li
mesh_terms: D000091306:Angiopoietin-Like Protein 8; D000075802:Angiopoietin-like Proteins; D000818:Animals; D001483:Base Sequence; D000071161:Forkhead Box Protein O1 / Q000378:metabolism*; D055786:Gene Knockout Techniques; D005943:Gluconeogenesis / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D006003:Glycogen / Q000096:biosynthesis; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism*; D056945:Hep G2 Cells; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D036361:Peptide Hormones / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000069896:Transcription Activator-Like Effector Nucleases; D014162:Transfection; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: C576683:ANGPTL8 protein, human; D000091306:Angiopoietin-Like Protein 8; D000075802:Angiopoietin-like Proteins; C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D007328:Insulin; D036361:Peptide Hormones; D012333:RNA, Messenger; D006003:Glycogen; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; D000069896:Transcription Activator-Like Effector Nucleases; D005947:Glucose
keywords: ANGPTL8/betatrophin; Akt; FoxO1; GSK3β; HepG2 cells; Insulin resistance