Periodontitis is a critical risk factor for the occurrence and development of diabetes. Porphyromonas gingivalis may participate in insulin resistance (IR) caused by periodontal inflammation, but the functional role and specific mechanisms of P. gingivalis in IR remain unclear. In the present study, clinical samples were analysed to determine the statistical correlation between P. gingivalis and IR occurrence. Through culturing of hepatocytes, myocytes, and adipocytes, and feeding mice P. gingivalis orally, the functional correlation between P. gingivalis and IR occurrence was further studied both in vitro and in vivo. Clinical data suggested that the amount of P. gingivalis isolated was correlated with the Homeostatic Model Assessment for IR score. In vitro studies suggested that coculture with P. gingivalis decreased glucose uptake and insulin receptor (INSR) protein expression in hepatocytes, myocytes, and adipocytes. Mice fed P. gingivalis tended to undergo IR. P. gingivalis was detectable in the liver, skeletal muscle, and adipose tissue of experimental mice. The distribution sites of gingipain coincided with the downregulation of INSR. Gingipain proteolysed the functional insulin-binding region of INSR. Coculture with P. gingivalis significantly decreased the INSR-insulin binding ability. Knocking out gingipain from P. gingivalis alleviated the negative effects of P. gingivalis on IR in vivo. Taken together, these findings indicate that distantly migrated P. gingivalis may directly proteolytically degrade INSR through gingipain, thereby leading to IR. The results provide a new strategy for preventing diabetes by targeting periodontal pathogens and provide new ideas for exploring novel mechanisms by which periodontal inflammation affects the systemic metabolic state.

中文翻译：

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来自牙龈卟啉单胞菌的牙龈蛋白酶通过直接蛋白水解作用降解胰岛素受体，从而引起胰岛素抵抗。


牙周炎是糖尿病发生和发展的重要危险因素。牙龈卟啉单胞菌可能参与牙周炎症引起的胰岛素抵抗（IR），但其在IR中的功能作用和具体机制仍不清楚。在本研究中，对临床样本进行了分析，以确定牙龈卟啉单胞菌与 IR 发生之间的统计相关性。通过培养肝细胞、肌细胞和脂肪细胞，并给小鼠口服牙龈卟啉单胞菌，在体外和体内进一步研究牙龈卟啉单胞菌与IR发生的功能相关性。临床数据表明，分离出的牙龈卟啉单胞菌的量与 IR 评分的稳态模型评估相关。体外研究表明，与牙龈卟啉单胞菌共培养可降低肝细胞、肌细胞和脂肪细胞中的葡萄糖摄取和胰岛素受体 (INSR) 蛋白表达。喂食牙龈卟啉单胞菌的小鼠往往会发生IR。在实验小鼠的肝脏、骨骼肌和脂肪组织中可检测到牙龈卟啉单胞菌。 gingipain的分布位点与INSR的下调一致。 Gingipain 蛋白水解 INSR 的功能性胰岛素结合区。与牙龈卟啉单胞菌共培养显着降低了INSR-胰岛素结合能力。从牙龈卟啉单胞菌中敲除牙龈蛋白酶减轻了牙龈卟啉单胞菌对体内IR的负面影响。综上所述，这些发现表明远距离迁移的牙龈卟啉单胞菌可能通过牙龈蛋白酶直接蛋白水解降解 INSR，从而导致 IR。 该结果为针对牙周病原菌预防糖尿病提供了新策略，并为探索牙周炎症影响全身代谢状态的新机制提供了新思路。