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,...
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Published in | International journal of oral science Vol. 16; no. 1; pp. 53 - 14 |
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Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
London
Nature Publishing Group UK
01.08.2024
Springer Nature B.V Nature Publishing Group |
Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 2049-3169 1674-2818 2049-3169 |
DOI: | 10.1038/s41368-024-00313-z |