Gingipain from Porphyromonas gingivalis causes insulin resistance by degrading insulin receptors through direct proteolytic effectsOACSTPCD
Gingipain from Porphyromonas gingivalis causes insulin resistance by degrading insulin receptors through direct proteolytic effects
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.
Fen Liu;Buling Wu;Bofeng Zhu;Ying An;Zhifei Zhou;Peiying Xiong;Xuan Li;Yang Mi;Tongqiang He;Faming Chen
Shenzhen Stomatology Hospital(Pingshan),Southern Medical University,Shenzhen,China||Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research,Laboratory Center of Stomatology,Department of Paediatric Dentistry,College of Stomatology,Xi'an Jiaotong University,Xi'an,China||State Key Laboratory of Oral&Maxillofacial Reconstruction and Regeneration,National Clinical Research Center for Oral Diseases,Shaanxi International Joint Research Center for Oral Diseases,Department of Periodontology,School of Stomatology,The Fourth Military Medical University,Xi'an,ChinaShenzhen Stomatology Hospital(Pingshan),Southern Medical University,Shenzhen,ChinaGuangzhou Key Laboratory of Forensic Multi-Omics for Precision Identification,School of Forensic Medicine,Southern Medical University,Guangzhou,China||Microbiome Medicine Center,Department of Laboratory Medicine,Zhujiang Hospital,Southern Medical University,Guangzhou,ChinaState Key Laboratory of Oral&Maxillofacial Reconstruction and Regeneration,National Clinical Research Center for Oral Diseases,Shaanxi International Joint Research Center for Oral Diseases,Department of Periodontology,School of Stomatology,The Fourth Military Medical University,Xi'an,ChinaDepartment of Stomatology,General Hospital of Tibetan Military Command,Lhasa,ChinaDepartment of Stomatology Center,Shenzhen Hospital,Southern Medical University,Shenzhen,ChinaDepartment of Obstetrics,Northwest Women's and Children's Hospital,Xi'an,China
《国际口腔科学杂志（英文版）》 2024 (003)
539-552 / 14
This study was supported by the Major Research Program of the National Natural Science Foundation of China(Subproject No.81991503);the Youth Research Program of the National Natural Science Foundation of China(No.82201069);the Innovative Talent Promotion Plan of Shaanxi Province-Research Fund for Young Star of Science and Technology(No.2021KJXX-24,No.2022KJXX-100);Basic and Applied Basic Research Fund of Guangdong Province(No.2023A1515012126).
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