Journal
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
Volume 1866, Issue 6, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.bbadis.2020.165731
Keywords
Outer membrane vesicles; Periodontal disease; Diabetes mellitus; Porphyromonas gingivalis; Insulin resistance
Funding
- Ministry of Education, Science, Sports, and Culture of Japan [16K11506, 17K11642]
- SHISEIKAI Scientific Award
- Kobayashi Magobe Memorial Medical Foundation
- Suzuken Memorial Foundation
- Shiseikai Association
- Grants-in-Aid for Scientific Research [17K11642, 16K11506] Funding Source: KAKEN
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Outer membrane vesicles (OMVs) are nanosized particles derived from the outer membrane of gram-negative bacteria. Oral bacterium Porphyromonas gingivalis (Pg) is known to be a major pathogen of periodontitis that contributes to the progression of periodontal disease by releasing OMVs. The effect of Pg OMVs on systemic diseases is still unknown. To verify whether Pg OMVs affect the progress of diabetes mellitus, we analyzed the cargo proteins of vesicles and evaluated their effect on hepatic glucose metabolism. Here, we show that Pg OMVs were equipped with Pg-derived proteases gingipains and translocated to the liver in mice. In these mice, the hepatic glycogen synthesis in response to insulin was decreased, and thus high blood glucose levels were maintained. Pg OMVs also attenuated the insulin-induced Akt/glycogen synthase kinase-3 beta (GSK-3 beta) signaling in a gingipain-dependent fashion in hepatic HepG2 cells. These results suggest that the delivery of gingipains mediated by Pg OMV elicits changes in glucose metabolisms in the liver and contributes to the progression of diabetes mellitus.
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