Diabetes fuels periodontal lesions via GLUT1-driven macrophage inflammaging.

Abstract

Hyperglycemia induces chronic low-grade inflammation (inflammaging), which is a newly identified contributor to diabetes-related tissue lesions, including the inflammatory bone loss in periodontitis. It is also a secondary senescent pattern mediated by an increased burden of senescent cells and senescence-associated secretory phenotype (SASP). Macrophage is a key SASP-spreading cell and may contribute to the maintenance of SASP response in the periodontal microenvironment. Using a transgenic diabetic model (BLKS/J-Leprdb/leprdb mice) we identified striking senescence of the periodontium in young (18-wk)-diabetic mice accompanied by amassed p16+-macrophages and enhanced early SASP response. Exposed to high glucose in vitro, bone marrow-derived macrophage (BMDM) revealed a strong GLUT1 mRNA response driving the elevated-glucose uptake. GLUT1 is a representative and facilitative glucose transporter in macrophages with potential roles in hyperglycemia-induced inflammation. In this study, both GLUT1 and the downstream GTPase Rheb expression upregulated in the gingiva of diabetic mice with impaired condition. Furthermore, SASP release and p16/p21 signaling were proven to be triggered by mTOR phosphorylation in BMDM and antagonized by restricting glucose uptake in GLUT1-/- BMDM. Taken together, our findings suggest that elevated-GLUT1 sensor responded to high glucose is important for macrophage senescence and SASP response, generated as a result of hyperglycemia, and it is a potential molecular mechanism for the exacerbation of periodontitis in diabetes.

• Authors: Qian Wang, Lulingxiao Nie, Pengfei Zhao, Xinyi Zhou, Yi Ding, Qianming Chen, Qi Wang
• Journal: International journal of oral science (Int J Oral Sci) Vol. 13 Issue 1 Pg. 11 (03 24 2021) ISSN: 2049-3169 [Electronic] India
• PMID: 33762572 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Glucose Transporter Type 1

Topics

• Animals
• Cellular Senescence
• Diabetes Mellitus, Experimental
• Glucose Transporter Type 1
• Inflammation
• Macrophages
• Mice