RRC ID 58773
Author Seyama M, Yoshida K, Yoshida K, Fujiwara N, Ono K, Eguchi T, Kawai H, Guo J, Weng Y, Haoze Y, Uchibe K, Ikegame M, Sasaki A, Nagatsuka H, Okamoto K, Okamura H, Ozaki K.
Title Outer membrane vesicles of Porphyromonas gingivalis attenuate insulin sensitivity by delivering gingipains to the liver.
Journal Biochim Biophys Acta Mol Basis Dis
Abstract 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 β (GSK-3β) 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.
Volume 1866(6)
Pages 165731
Published 2020-6-1
DOI 10.1016/j.bbadis.2020.165731
PII S0925-4439(20)30076-4
PMID 32088316
MeSH Animals Bacterial Outer Membrane / metabolism* Bacterial Outer Membrane / pathology Disease Models, Animal Gingipain Cysteine Endopeptidases / genetics* Gingipain Cysteine Endopeptidases / metabolism Glycogen Synthase Kinase 3 beta / genetics Humans Insulin Resistance / genetics Liver / metabolism Liver / microbiology Mice Periodontitis / genetics* Periodontitis / microbiology Periodontitis / pathology Porphyromonas gingivalis / genetics* Porphyromonas gingivalis / metabolism Porphyromonas gingivalis / pathogenicity Proto-Oncogene Proteins c-akt / genetics Signal Transduction / genetics
IF 4.328
Times Cited 2
Human and Animal Cells Hep G2(RCB1886)