title: Periodontitis aggravated pancreatic β-cell dysfunction in diabetic mice through interleukin-12 regulation on Klotho.
abstract: OBJECTIVE
  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 β-cells with pro-inflammatory cytokines-related immune mechanism in a mouse model.
  
  
  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 β-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 β-cell failure, with insulin resistance, was observed in db/db mice, while periodontitis could aggravate β-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 β-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 β-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 β-cell function in diabetes.
authors.affiliation: Department of Stomatology Affiliated Hospital of Inner Mongolia University For The Nationalities Inner Mongolia Tongliao China.
authors.forename: Yihua
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Ophthalmology Affiliated Hospital of Inner Mongolia University For The Nationalities Inner Mongolia Tongliao China.
authors.forename: Qiuli
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001786:Blood Glucose; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism; D048909:Diabetes Complications / Q000378:metabolism*; D004195:Disease Models, Animal; D005966:Glucuronidase / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D018664:Interleukin-12 / Q000378:metabolism*; D000090265:Klotho Proteins; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010518:Periodontitis / Q000150:complications / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D016207:Cytokines; D018836:Inflammation Mediators; D007328:Insulin; D018664:Interleukin-12; D005966:Glucuronidase; D000090265:Klotho Proteins
keywords: Klotho; Pancreatic β‐cell; Periodontitis