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-Lepr^db/lepr^db 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.

高血糖会诱发慢性低度炎症（炎症），这是新发现的导致糖尿病相关组织损伤的因素，包括牙周炎中的炎症性骨质流失。它也是一种由衰老细胞负担增加和衰老相关分泌表型 (SASP) 介导的继发性衰老模式。巨噬细胞是一种关键的 SASP 传播细胞，可能有助于维持牙周微环境中的 SASP 反应。使用转基因糖尿病模型（BLKS/J- Lepr ^db / lepr ^db小鼠），我们发现年轻（18 周）糖尿病小鼠的牙周组织明显衰老，并伴有 p16 ^+积累-巨噬细胞和增强的早期 SASP 反应。在体外暴露于高葡萄糖的情况下，骨髓来源的巨噬细胞 (BMDM) 显示出强烈的 GLUT1 mRNA 反应，驱动葡萄糖摄取升高。GLUT1 是巨噬细胞中具有代表性和促进性的葡萄糖转运蛋白，在高血糖引起的炎症中具有潜在作用。在这项研究中，GLUT1 和下游 GTPase Rheb 表达在受损的糖尿病小鼠牙龈中上调。此外，SASP 释放和 p16/p21 信号被证明由 BMDM 中的 mTOR 磷酸化触发，并通过限制GLUT1中的葡萄糖摄取来拮抗^{- /-}BMDM。综上所述，我们的研究结果表明，升高的 GLUT1 传感器对高血糖的反应对于巨噬细胞衰老和 SASP 反应很重要，这是由高血糖引起的，它是糖尿病患者牙周炎恶化的潜在分子机制。