title: Periodontal disease decreases insulin sensitivity and insulin signaling.
abstract: BACKGROUND
  The purpose of this study is to investigate whether local inflammatory events, such as periodontal disease, are able to increase tumor necrosis factor-alpha (TNF-α) plasmatic concentration and decrease insulin sensitivity and insulin signaling in non-diabetic rats.
  
  
  METHODS
  Forty-eight male Wistar rats (2 months old) were divided into two groups, with either ligature-induced periodontal disease (LPD) or control conditions (CN). Experiments were performed in both groups 28 days after ligature placement. Plasmatic concentration of glycemia and TNF-α (n = 10) were analyzed by the glucose oxidase and enzyme-linked immunosorbent assay method, respectively. Insulin sensitivity (n = 7) was measured using the insulin tolerance test. Insulin signal transduction (n = 7) was measured by pp185 tyrosine phosphorylation status in insulin-sensitive tissues using the Western blotting method.
  
  
  RESULTS
  The LPD group showed decreased insulin sensitivity (P <0.05), although no glycemic alterations were noted (P >0.05). TNF-α plasmatic concentration was higher in LPD rats compared to CN rats. In addition, a decrease in the pp185 tyrosine phosphorylation status was observed after insulin stimulus in both white adipose and skeletal muscle tissues of the LPD group compared with the CN group.
  
  
  CONCLUSIONS
  LPD is able to cause alterations to both insulin signaling and insulin sensitivity, probably because of the elevation of TNF-α plasmatic concentration. Thus, the present results emphasize the importance of the prevention of local inflammatory diseases, such as periodontitis, to prevent diabetes mellitus.
authors.affiliation: Department of Basic Sciences, Dental School of Araçatuba, Univ Estadual Paulista-UNESP (São Paulo State University), São Paulo, São Paulo, Brazil.
authors.forename: Natalia H
authors.initials: NH
authors.lastname: Colombo
authors.forename: Daisy J
authors.initials: DJ
authors.lastname: Shirakashi
authors.forename: Fernando Y
authors.initials: FY
authors.lastname: Chiba
authors.forename: Maria Sara de Lima
authors.initials: MS
authors.lastname: Coutinho
authors.forename: Edilson
authors.initials: E
authors.lastname: Ervolino
authors.forename: Cléa Adas Saliba
authors.initials: CA
authors.lastname: Garbin
authors.forename: Ubiratan Fabres
authors.initials: UF
authors.lastname: Machado
authors.forename: Doris H
authors.initials: DH
authors.lastname: Sumida
mesh_terms: D052438:Adipocytes, White / Q000187:drug effects / Q000201:enzymology; D016301:Alveolar Bone Loss / Q000000981:diagnostic imaging / Q000473:pathology; D000539:Alveolar Process / Q000000981:diagnostic imaging / Q000473:pathology; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D005889:Gingival Recession / Q000473:pathology; D007328:Insulin / Q000097:blood* / Q000494:pharmacology; D055504:Insulin Receptor Substrate Proteins / Q000494:pharmacology; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000201:enzymology; D010518:Periodontitis / Q000097:blood* / Q000473:pathology; D010766:Phosphorylation; D011859:Radiography; D051381:Rats; D017208:Rats, Wistar; D011972:Receptor, Insulin / Q000187:drug effects; D015398:Signal Transduction / Q000502:physiology*; D019237:Tooth Cervix / Q000000981:diagnostic imaging / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*
chemical_list: D001786:Blood Glucose; C526292:IRS1 protein, human; C526297:IRS2 protein, human; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D014409:Tumor Necrosis Factor-alpha; D011972:Receptor, Insulin