title: Porphyromonas gingivalis attenuates the insulin-induced phosphorylation and translocation of forkhead box protein O1 in human hepatocytes.
abstract: OBJECTIVE
  Porphyromonas gingivalis (P. gingivalis) is a pathogen involved in periodontal disease. Recently, periodontal disease has been demonstrated to increase the risk of developing diabetes mellitus, although the molecular mechanism is not fully understood. Forkhead box protein O1 (FoxO1) is a transcriptional factor that regulates gluconeogenesis in the liver. Gluconeogenesis is a key process in the induction of diabetes mellitus; however, little is known regarding the relationship between periodontal disease and gluconeogenesis. In this study, to investigate whether periodontal disease influences hepatic gluconeogenesis, we examined the effects of P. gingivalis on the phosphorylation and translocation of FoxO1 in insulin-induced human hepatocytes.
  
  
  METHODS
  The human hepatocyte HepG2 was treated with insulin and Akt and FoxO1 phosphorylation was detected by western blot analysis. The localization of phosphorylated FoxO1 was detected by immunocytochemistry and western blot analysis. HepG2 cells were treated with SNAP26b-tagged P. gingivalis (SNAP-P.g.) before insulin stimulation, and then the changes in Akt and FoxO1 were determined by western blot analysis and immunocytochemistry.
  
  
  RESULTS
  Insulin (100nM) induced FoxO1 phosphorylation 60min after treatment in HepG2 cells. Phosphorylated FoxO1 translocated to the cytoplasm. SNAP-P.g. internalized into HepG2 cells and decreased Akt and FoxO1 phosphorylation induced by insulin. The effect of insulin on FoxO1 translocation was also attenuated by SNAP-P.g.
  
  
  CONCLUSIONS
  Our study shows that P. gingivalis decreases the phosphorylation and translocation of FoxO induced by insulin in HepG2 cells. Our results suggest that periodontal disease may increase hepatic gluconeogenesis by reducing the effects of insulin on FoxO1.
authors.affiliation: Departments of Oral Healthcare Promotion, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto, Tokushima 770-8504, Japan.
authors.forename: Haruna
authors.initials: H
authors.lastname: Takamura
authors.affiliation: Departments of Oral Healthcare Education, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto, Tokushima 770-8504, Japan. Electronic address: kaya@tokushima-u.ac.jp.
authors.forename: Kaya
authors.initials: K
authors.lastname: Yoshida
authors.affiliation: Departments of Histology and Oral Histology, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto, Tokushima 770-8504, Japan.
authors.forename: Hirohiko
authors.initials: H
authors.lastname: Okamura
authors.affiliation: Departments of Oral Healthcare Promotion, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto, Tokushima 770-8504, Japan.
authors.forename: Natsumi
authors.initials: N
authors.lastname: Fujiwara
authors.affiliation: Departments of Oral Healthcare Promotion, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto, Tokushima 770-8504, Japan.
authors.forename: Kazumi
authors.initials: K
authors.lastname: Ozaki
mesh_terms: D015153:Blotting, Western / Q000379:methods; D000071161:Forkhead Box Protein O1 / Q000494:pharmacology*; D005943:Gluconeogenesis / Q000187:drug effects; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism / Q000382:microbiology*; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D010510:Periodontal Diseases / Q000150:complications / Q000382:microbiology; D010766:Phosphorylation / Q000187:drug effects; D016966:Porphyromonas gingivalis / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D007328:Insulin
keywords: Diabetes mellitus; Forkhead box protein O1 (FoxO1); Periodontal disease; Porphyromonas gingivalis