the glucagon-like peptide-1 (glp-1) receptor agonist liraglutide regulates sirtuin-1-mediated neutrophil extracellular traps to improve diabetes-induced bone metabolism imbalance

Background: diabetes mellitus (dm) is a chronic metabolic disorder that disrupts normal bone remodeling.objectives: this study aimed to investigate how the glucagon-like peptide-1 (glp-1) receptor agonist liraglutide (lir) addresses bone metabolism imbalances induced by type-ii diabetes. methods: type-ii diabetic rat models were established through a single intraperitoneal injection of streptozotocin (stz). blood glucose levels were measured using a blood glucose meter, and insulin levels were assessed using an assay kit. bone formation markers [alkaline phosphatase (alp), osteocalcin (ocn), and procollagen i n-terminal propeptide (pinp)] and bone resorption markers [tartrate-resistant acid phosphatase (tracp) and ctx-1] were monitored using assay kits. bone marrow mesenchymal stem cells (bmscs) were cultured in vitro under high-fat and high-glucose (hfhs) conditions to mimic diabetic bone metabolism dysregulation. neutrophil extracellular traps (nets) formation was examined through immunofluorescent staining and western blot analysis. results: liraglutide was found to reduce stz-induced nets formation, as indicated by decreased expression of cit-h3 by 36.90% - 53.57%, myeloperoxidase (mpo) by 55.81% - 65.12%, ne by 53.95% - 65.17%, and pad4 by 46.81% - 63.83%, alongside increased sirtuin-1 (sirt1) expression in femur tissue (70.71% - 91.19%). in vitro, lir enhanced osteogenesis and inhibited apoptosis, effects that were partially reversed by sirt1 knockdown. additionally, sirt1 knockdown partially restored lir-induced reductions in oxidative stress, inflammation, and nets formation. conclusions: lir mitigates diabetes-induced bone metabolism imbalance by inhibiting nets formation through sirt1 mediation.