The role of AMPK inactivation in mediating high glucose-induced secretion of inflammatory factors by macrophages in diabetes-related periodontitis

ZHU Ke; JIANG Jihua; SHENG Peng; WANG Xin

doi:10.15956/j.cnki.chin.j.conserv.dent.2026.02.003

Abstract：Objective To investigate the differential impacts of hyperglycemic microenvironment and oral microbiota on pro-inflammatory cytokine secretion by macrophages in diabetes-associated periodontitis.Methods Oral saliva microbiota extracts from patients with periodontitis and diabetes were collected and used to stimulate THP-1-induced macrophages.The expression of inflammatory factors in macrophages was then detected by RT-PCR,with normal blood glucose periodontitis patients as the control.Macrophages were stimulated with LPS under culture conditions with different glucose concentrations,and macrophage inflammatory factor expression was detected using RT-PCR.Changes in AMPK and phosphorylation levels were observed by protein blotting,TNF-α expression was detected by flow cytometry.M0 macrophages were transfected with si-AMPKα to reduce AMPK expression,and IL-6 and TNF-α expression was detected by RT-PCR,IL-1β expression.Results The effect of microbial culture on macrophage inflammatory factor expression in the hyperglycemic group was not significantly different from that in the control group.The high glucose microenvironment significantly enhanced the inflammatory response,with the greatest difference in TNF-α expression.Different glucose levels had no significant effect on the overall AMPK protein level,but low glucose can stimulate an increase in the phosphorylation level of AMPKα(Thr172),and reduce the secretion of inflammatory factors.Conclusion No regulatory effect of microbiota differences on the secretion of selected pro-inflammatory factors by macrophages was observed in patients with periodontitis related to diabetes.The high glucose microenvironment induces M1 polarization of macrophages by inhibiting AMPK phosphorylation,significantly amplifying the inflammatory cascade reaction.