Oral Porphyromonas gingivalis translocates to the liver and regulates hepatic glycogen synthesis through the Akt/GSK-3β signaling pathway

Makoto Ishikawa, Kaya Yoshida, Hirohiko Okamura, Kazuhiko Ochiai, Haruna Takamura, Natsumi Fujiwara, Kazumi Ozaki

Research output: Contribution to journalArticle

36 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2035-2043
Number of pages9
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1832
Issue number12
DOIs
Publication statusPublished - Dec 1 2013
Externally publishedYes

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Keywords

  • Diabetes mellitus
  • Hepatic glycogenesis
  • Periodontal disease
  • Porphyromonas gingivalis
  • SNAP26b

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology

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