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.

中文翻译：

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牙龈卟啉单胞菌的外膜囊泡通过将姜黄素递送至肝脏来减弱胰岛素敏感性。

外膜囊泡（OMV）是源自革兰氏阴性细菌外膜的纳米级颗粒。口腔细菌齿龈卟啉单胞菌（Pg）被认为是牙周炎的主要病原体，它通过释放OMV促进牙周疾病的发展。Pg OMV对全身性疾病的影响仍然未知。为了验证Pg OMV是否会影响糖尿病的进展，我们分析了囊泡的货物蛋白并评估了其对肝糖代谢的影响。在这里，我们显示Pg OMVs配备了Pg衍生的蛋白酶姜黄素，并在小鼠中转移到肝脏。在这些小鼠中，响应胰岛素的肝糖原合成减少，因此维持了高血糖水平。Pg OMV在肝HepG2细胞中也以姜黄素依赖性方式减弱了胰岛素诱导的Akt /糖原合酶激酶3β（GSK-3β）信号传导。这些结果表明，由Pg OMV介导的姜黄素的递送引起肝脏中葡萄糖代谢的变化，并有助于糖尿病的发展。