Periodontitis aggravated pancreatic beta-cell dysfunction in diabetic mice through interleukin-12 regulation on Klotho.

AIMS/INTRODUCTION: Recent studies have shown that periodontitis can contribute to adipose tissue inflammation and subsequent systemic insulin resistance in the obese rat model. However, the related inflammatory mechanism is not yet clear. The present study aims to investigate the effects of periodontitis on the function of pancreatic beta-cells with pro-inflammatory cytokines-related immune mechanism in a mouse model. MATERIALS AND METHODS: C57BL/6-db/db and inbred C57BL/6 mice were chosen here to establish a mouse model with periodontitis, which was induced by ligatures for 8 weeks. Glucose-stimulated insulin secretion was introduced to evaluate the function of pancreatic islets and beta-cells. Serum levels of pro-inflammatory cytokines and Klotho were also measured, and the correlation between immunostimulation and Klotho level was deeply investigated in vitro. RESULTS: Pancreatic beta-cell failure, with insulin resistance, was observed in db/db mice, while periodontitis could aggravate beta-cell dysfunction-related features. Serum levels of interleukin (IL)-12 and Klotho showed a negatively synergistic change, whereas the expression of Klotho was also inhibited under IL-12 treatment in MIN6 beta-cells or isolated islets. Furthermore, IL-12-induced immune stimulation and also decreased insulin secretion were proven to be reversed by Klotho overexpression. CONCLUSIONS: Periodontitis aggravated pancreatic beta-cell failure in diabetic mice. Further in vitro studies showed IL-12 regulation on Klotho, while Klotho also acted as an inhibitor on IL-12, indicating the potential of Klotho for preserving pancreatic beta-cell function in diabetes.