title: Periapical lesions decrease insulin signal and cause insulin resistance.
abstract: BACKGROUND
  Inflammatory cytokines are associated with decreased insulin signal transduction. Moreover, local oral inflammation, such as that accompanying periodontal disease, is associated with insulin resistance and type 2 diabetes mellitus. The aim of this study was to evaluate the effect of periapical lesions (PLs) on insulin signaling and insulin sensitivity in rats. We hypothesized that PLs alter systemic insulin signaling and insulin sensitivity via elevated plasmatic tumor necrosis factor α (TNF-α).
  
  
  METHODS
  Wistar rats were divided into control (CN) and PL groups. PLs were induced by exposing pulpal tissue to the oral environment. After 30 days, insulin sensitivity was measured using the insulin tolerance test. After euthanization, maxillae were processed for histopathology. Plasmatic concentrations of tumor necrosis factor α (TNF-α) were determined via the enzyme-linked immunosorbent assay. Insulin signal transduction was evaluated using insulin receptor substrate tyrosine phosphorylation status and serine phosphorylation status in periepididymal white adipose tissue via Western blotting. For insulin signaling and insulin tolerance tests, the analyses performed were analysis of variance followed by the Tukey post hoc test. For TNF-α analysis, the Student's t test was used. In all tests, P < .05 was considered significant.
  
  
  RESULTS
  The rats with PLs showed higher plasmatic TNF-α, lower constant rate for glucose disappearance values, and reduced pp185 tyrosine phosphorylation status but no change in serine phosphorylation status in white adipose tissue after insulin stimulation.
  
  
  CONCLUSIONS
  PLs can cause alterations to both insulin signaling and insulin sensitivity, probably because of elevation of plasmatic TNF-α. The results from this study emphasize the importance of the prevention of local inflammatory diseases, such as PLs, with regard to the prevention of insulin resistance.
authors.affiliation: Basic Sciences, Araçatuba Dental School, UNESP-Universidade Estadual Paulista, Araçatuba, Sao Paulo, Brazil.
authors.forename: Rafael Dias
authors.initials: RD
authors.lastname: Astolphi
authors.forename: Mariane Machado
authors.initials: MM
authors.lastname: Curbete
authors.forename: Natalia Helena
authors.initials: NH
authors.lastname: Colombo
authors.forename: Daisy Jaqueline
authors.initials: DJ
authors.lastname: Shirakashi
authors.forename: Fernando Yamamoto
authors.initials: FY
authors.lastname: Chiba
authors.forename: Annelise Katrine Carrara
authors.initials: AK
authors.lastname: Prieto
authors.forename: Luciano Tavares Angelo
authors.initials: LT
authors.lastname: Cintra
authors.forename: Suely Regina Mogami
authors.initials: SR
authors.lastname: Bomfim
authors.forename: Edilson
authors.initials: E
authors.lastname: Ervolino
authors.forename: Doris Hissako
authors.initials: DH
authors.lastname: Sumida
mesh_terms: D052436:Adipose Tissue, White / Q000473:pathology; D000818:Animals; D003789:Dental Pulp Exposure / Q000150:complications; D003790:Dental Pulp Necrosis / Q000150:complications; D007328:Insulin / Q000097:blood / Q000502:physiology*; D055504:Insulin Receptor Substrate Proteins / Q000032:analysis; D007333:Insulin Resistance / Q000502:physiology*; D007963:Leukocytes, Mononuclear / Q000473:pathology; D008297:Male; D009504:Neutrophils / Q000473:pathology; D010483:Periapical Diseases / Q000097:blood / Q000503:physiopathology*; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D011972:Receptor, Insulin / Q000032:analysis; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014443:Tyrosine / Q000378:metabolism
chemical_list: D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D014409:Tumor Necrosis Factor-alpha; D014443:Tyrosine; D012694:Serine; D011972:Receptor, Insulin