IADR Abstract Archives
Periodontitis Related Circulating Small Extracellular Vesicles Foster Diabetic Pathology
Objectives: Epidemiological studies have identified the role of periodontitis in the pathogenesis of type 2 diabetes, but the underlying mechanism is poorly understood. The purpose of this study was to investigate whether periodontitis induces or exacerbates insulin resistance, the primary mechanism of type 2 diabetic pathology, via small extracellular vesicles derived from plasma.
Methods: Type 2 diabetic rat was established by high-fat diet nourishment followed by streptozotocin injection, and periodontitis rat was established by ligation combined with bacterial inoculation. Plasma small extracellular vesicles from control and periodontitis rats were intravenously injected into type 2 diabetic rats (n=6). Insulin tolerance tests, glucose tolerance tests and the activation of the insulin signaling pathway were measured to detect the effect of the plasma small extracellular vesicles on insulin sensitivity. In addition, plasma small extracellular vesicles from periodontitis patients with or without type 2 diabetes were isolated, and their cellular effects on insulin resistance were investigated in vitro.
Results: Plasma small extracellular vesicles derived from periodontitis rats further impaired glucose tolerance and insulin tolerance in type 2 diabetic rats and significantly reduced the activation of the insulin signaling pathway in liver tissues, as evidenced by the decreased levels of p-AKT and p-GSK3β and the reduced hepatic glycogen content. For small extracellular vesicles isolated from human plasma, the concentration of small extracellular vesicles in patients with type 2 diabetes combined with periodontitis was higher than that of the healthy control and periodontitis alone. Moreover, plasma-derived small extracellular vesicles from patients with periodontitis significantly inhibited the glucose uptake capacity of HepG2 cells and inhibited insulin signaling in vitro.
Conclusions: These results highlight that plasma sEVs played a critical role in periodontitis aggravating insulin resistance. In addition to periodontal treatment, plasma small extracellular vesicles could be modified or neutralized as another promising shortcut to interfere with the adverse effect of periodontitis on diabetes.
Methods: Type 2 diabetic rat was established by high-fat diet nourishment followed by streptozotocin injection, and periodontitis rat was established by ligation combined with bacterial inoculation. Plasma small extracellular vesicles from control and periodontitis rats were intravenously injected into type 2 diabetic rats (n=6). Insulin tolerance tests, glucose tolerance tests and the activation of the insulin signaling pathway were measured to detect the effect of the plasma small extracellular vesicles on insulin sensitivity. In addition, plasma small extracellular vesicles from periodontitis patients with or without type 2 diabetes were isolated, and their cellular effects on insulin resistance were investigated in vitro.
Results: Plasma small extracellular vesicles derived from periodontitis rats further impaired glucose tolerance and insulin tolerance in type 2 diabetic rats and significantly reduced the activation of the insulin signaling pathway in liver tissues, as evidenced by the decreased levels of p-AKT and p-GSK3β and the reduced hepatic glycogen content. For small extracellular vesicles isolated from human plasma, the concentration of small extracellular vesicles in patients with type 2 diabetes combined with periodontitis was higher than that of the healthy control and periodontitis alone. Moreover, plasma-derived small extracellular vesicles from patients with periodontitis significantly inhibited the glucose uptake capacity of HepG2 cells and inhibited insulin signaling in vitro.
Conclusions: These results highlight that plasma sEVs played a critical role in periodontitis aggravating insulin resistance. In addition to periodontal treatment, plasma small extracellular vesicles could be modified or neutralized as another promising shortcut to interfere with the adverse effect of periodontitis on diabetes.