title: Berberine reduces endoplasmic reticulum stress and improves insulin signal transduction in Hep G2 cells.
abstract: OBJECTIVE
  Endoplasmic reticulum (ER) stress plays an important role in the pathogenesis of insulin resistance and pancreatic beta-cell dysfunction. The aim of this study is to investigate whether the insulin-sensitizing action of berberine is related to reducing ER stress.
  
  
  METHODS
  ER stress in cultured Hep G2 cells was induced with tunicamycin. Cells were pretreated with berberine in combination with or without insulin. The concentration of glucose was measured by glucose oxidase method. The molecular markers of ER stress, including ORP150, PERK, and eIF2 alpha were analyzed by Western blot or real time PCR. The activity of JNK was also evaluated. Moreover, the insulin signaling proteins such as IRS-1 and AKT were determined by Western blot.
  
  
  RESULTS
  The production of glucose stimulated with insulin was reduced. The expressions of ORP150 was decreased both in gene and protein levels when cells were pretreated with berberine, while the activation of JNK was blocked. The levels of phosphorylation both on PERK and eIF2 alpha were inhibited in cells pretreated with berberine. The level of IRS-1 ser(307) phosphorylation was decreased, whereas IRS-1 tyr phosphorylation was increased notablely. AKT ser(473) phosphorylation was also enhanced significantly in the presence of berberine.
  
  
  CONCLUSIONS
  The antidiabetic effect of berberine in Hep G2 cells maybe related to attenuation of ER stress and improvement of insulin signal transduction.
authors.affiliation: Institute of Integrative Traditional Chinese & Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan 430030, China.
authors.forename: Zeng-si
authors.initials: ZS
authors.lastname: Wang
authors.forename: Fu-er
authors.initials: FE
authors.lastname: Lu
authors.forename: Li-jun
authors.initials: LJ
authors.lastname: Xu
authors.forename: Hui
authors.initials: H
authors.lastname: Dong
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000998:Antiviral Agents / Q000494:pharmacology*; D001599:Berberine / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004721:Endoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D015398:Signal Transduction / Q000187:drug effects*; D014415:Tunicamycin / Q000494:pharmacology
chemical_list: D000893:Anti-Inflammatory Agents; D000998:Antiviral Agents; D007328:Insulin; D001599:Berberine; D014415:Tunicamycin; D005947:Glucose
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