title: Resistin induces insulin resistance, but does not affect glucose output in rat-derived hepatocytes.
abstract: OBJECTIVE
  The aim of the present study was to observe the effects of resistin on insulin sensitivity and glucose output in rat-derived hepatocytes.
  
  
  METHODS
  The rat hepatoma cell line H4IIE was cultured and stimulated with resistin; supernant glucose and glycogen content were detected. The insulin receptor substrate (IRS)-1 and IRS-2, protein kinase B/Akt, glycogen synthase kinase-3beta(GSK-3 beta), the suppressor of cytokine signaling 3 (SOCS-3) protein content, as well as the phosphorylation status were assessed by Western blotting. Specific antisense oligodeoxynucleotides directed against SOCS-3 were used to knockdown SOCS-3.
  
  
  RESULTS
  Resistin induced insulin resistance, but did not affect glucose output in rat hepatoma cell line H4IIE. Resistin attenuated multiple effects of insulin, including insulin-stimulated glycogen synthesis and phosphorylation of IRS, protein kinase B/Akt, as well as GSK-3beta. Resistin treatment markedly induced the gene and protein expression of SOCS-3, a known inhibitor of insulin signaling. Furthermore, a specific antisense oligodeoxynucleotide directed against SOCS-3 treatment prevented resistin from antagonizing insulin action.
  
  
  CONCLUSIONS
  The major function of resistin on liver is to induce insulin resistance. SOCS-3 induction may contribute to the resistin-mediated inhibition of insulin signaling in H4IIE hepatocytes.
authors.affiliation: Department of Pediatrics, Nanjing Maternity and Child Health Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
authors.forename: Tao
authors.initials: T
authors.lastname: Yang
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.forename: Nan
authors.initials: N
authors.lastname: Gu
authors.forename: Jie
authors.initials: J
authors.lastname: Qiu
authors.forename: Hong-qi
authors.initials: HQ
authors.lastname: Fan
authors.forename: Chun-mei
authors.initials: CM
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: Fei
authors.forename: Xiao-qing
authors.initials: XQ
authors.lastname: Pan
authors.forename: Mei
authors.initials: M
authors.lastname: Guo
authors.forename: Rong-hua
authors.initials: RH
authors.lastname: Chen
authors.forename: Xi-rong
authors.initials: XR
authors.lastname: Guo
mesh_terms: D000818:Animals; D002460:Cell Line; D005947:Glucose / Q000378:metabolism*; D006003:Glycogen / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism*; D007329:Insulin Antagonists / Q000494:pharmacology; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D020320:Oligoribonucleotides, Antisense / Q000494:pharmacology; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D052243:Resistin / Q000494:pharmacology*; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism
chemical_list: D007329:Insulin Antagonists; D055504:Insulin Receptor Substrate Proteins; C526299:Irs2 protein, rat; D020320:Oligoribonucleotides, Antisense; D052243:Resistin; C491410:Socs3 protein, rat; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D012313:RNA; D006003:Glycogen; D005947:Glucose