title: Oral Porphyromonas gingivalis translocates to the liver and regulates hepatic glycogen synthesis through the Akt/GSK-3β signaling pathway.
abstract: Periodontal diseases are common chronic inflammatory disorders that result in the destruction of tissues around teeth. Many clinical studies suggest that periodontal diseases are risk factors for insulin resistance and diabetic mellitus development. However, the molecular mechanisms by which periodontal diseases regulate the progress of diabetes mellitus remain unknown. In this study, we investigated whether Porphyromonas gingivalis (P.g.), a major pathogen of periodontal diseases, present in the oral cavity, moves to the liver and affects hepatic glycogen synthesis. SNAP26b-tagged P.g. (SNAP-P.g.) was introduced into the oral cavity to induce periodontal disease in 4-week old female Balb/c mice. SNAP-P.g. was detected in the liver extracted from SNAP-P.g.-treated mice using nested PCR analysis. High blood glucose levels tended to promote SNAP-P.g. translocation from the oral cavity to the liver in mice. Periodic acid-Schiff staining suggested that hepatic glycogen synthesis decreased in SNAP-P.g.-treated mice. SNAP-P.g. was also internalized into the human hepatoma cell line HepG2, and this attenuated the phosphorylation of insulin receptor substrate (IRS)-1, Akt and glycogen synthase kinase-3β induced by insulin. Insulin-induced glycogen synthesis was suppressed by SNAP-P.g. in HepG2 cells. Our results suggest that P.g. translocation from the oral cavity to the liver may contribute to the progress of diabetes mellitus by influencing hepatic glycogenesis.
authors.affiliation: Department of Oral Healthcare Promotion, The University of Tokushima Graduate School, Kuramoto, Tokushima 770-8504, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Ishikawa
authors.forename: Kaya
authors.initials: K
authors.lastname: Yoshida
authors.forename: Hirohiko
authors.initials: H
authors.lastname: Okamura
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Ochiai
authors.forename: Haruna
authors.initials: H
authors.lastname: Takamura
authors.forename: Natsumi
authors.initials: N
authors.lastname: Fujiwara
authors.forename: Kazumi
authors.initials: K
authors.lastname: Ozaki
mesh_terms: D000818:Animals; D016866:Bacteroidaceae Infections / Q000150:complications* / Q000382:microbiology / Q000473:pathology; D015153:Blotting, Western; D005260:Female; D005881:Gingiva / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D056945:Hep G2 Cells; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D008112:Liver Glycogen / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009061:Mouth Mucosa / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D010518:Periodontitis / Q000209:etiology* / Q000473:pathology; D010766:Phosphorylation; D016966:Porphyromonas gingivalis / Q000472:pathogenicity*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050600:SNARE Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D055504:Insulin Receptor Substrate Proteins; D008112:Liver Glycogen; D012333:RNA, Messenger; D050600:SNARE Proteins; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3
keywords: Diabetes mellitus; Hepatic glycogenesis; Periodontal disease; Porphyromonas gingivalis; SNAP26b