title: Periapical Lesions Decrease Insulin Signaling in Rat Skeletal Muscle.
abstract: BACKGROUND
  Serum inflammatory cytokines derived from oral inflammation are associated with decreased insulin signaling (IS) and insulin resistance, which is a major risk factor for type 2 diabetes mellitus. This study aimed to investigate IS in the liver and skeletal muscle (SM) and disorders related to the serum lipid profile and glucose and insulin levels of nondiabetic rats with induced chronic periapical lesions (PLs).
  
  
  METHODS
  Twenty-eight Wistar rats were divided into control and PL groups. PLs were induced by exposing the pulpal tissue to the oral environment. Experiments were conducted in both groups 30 days after pulp exposure. Maxillae were processed for histopathological analysis. IS was evaluated according to insulin receptor substrate (pp185-insulin receptor substrate 1 [IRS-1]/insulin receptor substrate 2 [IRS-2]) tyrosine phosphorylation status, IRS-1 serine phosphorylation status, and IRS-1 and IRS-2 content in the liver and SM by Western blotting. Serum total cholesterol, triglyceride, glucose, and insulin levels were measured enzymatically using a commercial kit.
  
  
  RESULTS
  PL rats showed reduced pp185 P-Tyr and increased IRS-1 serine phosphorylation status in the SM but no change in the liver after insulin stimulation. No significant changes in IRS-1 and IRS-2 content, serum total cholesterol, triglyceride, glucose or insulin levels were noted.
  
  
  CONCLUSIONS
  PLs are associated with decreased insulin signaling in the SM of rats. Because a decrease in insulin signaling is associated with insulin resistance, our results emphasize the importance of preventing local inflammatory diseases such as PLs to prevent alterations in IS in muscle.
authors.affiliation: Department of Basic Sciences, Araçatuba Dental School, Universidade Estadual Paulista (UNESP), Araçatuba, São Paulo, Brazil.
authors.forename: Rafael Dias
authors.initials: RD
authors.lastname: Astolphi
authors.affiliation: Department of Basic Sciences, Araçatuba Dental School, Universidade Estadual Paulista (UNESP), Araçatuba, São Paulo, Brazil.
authors.forename: Mariane Machado
authors.initials: MM
authors.lastname: Curbete
authors.affiliation: Department of Basic Sciences, Araçatuba Dental School, Universidade Estadual Paulista (UNESP), Araçatuba, São Paulo, Brazil.
authors.forename: Fernando Yamamoto
authors.initials: FY
authors.lastname: Chiba
authors.affiliation: Department of Endodontics, Araçatuba Dental School, Araçatuba, São Paulo, Brazil.
authors.forename: Luciano Tavares Angelo
authors.initials: LT
authors.lastname: Cintra
authors.affiliation: Department of Basic Sciences, Araçatuba Dental School, Universidade Estadual Paulista (UNESP), Araçatuba, São Paulo, Brazil.
authors.forename: Edilson
authors.initials: E
authors.lastname: Ervolino
authors.affiliation: Department of Basic Sciences, Araçatuba Dental School, Universidade Estadual Paulista (UNESP), Araçatuba, São Paulo, Brazil.
authors.forename: Max Sander de Oliveira
authors.initials: MS
authors.lastname: da Mota
authors.affiliation: Department of Basic Sciences, Araçatuba Dental School, Universidade Estadual Paulista (UNESP), Araçatuba, São Paulo, Brazil.
authors.forename: Cristina
authors.initials: C
authors.lastname: Antoniali
authors.affiliation: Department of Child and Social Dentistry, Araçatuba Dental School, UNESP, Araçatuba, São Paulo, Brazil.
authors.forename: Cléa Adas Saliba
authors.initials: CA
authors.lastname: Garbin
authors.affiliation: Department of Basic Sciences, Araçatuba Dental School, Universidade Estadual Paulista (UNESP), Araçatuba, São Paulo, Brazil. Electronic address: dorishs@foa.unesp.br.
authors.forename: Doris Hissako
authors.initials: DH
authors.lastname: Sumida
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D002784:Cholesterol / Q000097:blood; D003782:Dental Pulp / Q000293:injuries* / Q000473:pathology; D004195:Disease Models, Animal; D006949:Hyperlipidemias / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D007328:Insulin / Q000378:metabolism; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D017208:Rats, Wistar; D014280:Triglycerides / Q000097:blood; D014443:Tyrosine / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; C526299:Irs2 protein, rat; D014280:Triglycerides; D014443:Tyrosine; D002784:Cholesterol
keywords: Insulin receptor substrate proteins; lipidemia; periapical lesions; skeletal muscle