title: JNK and IKKβ phosphorylation is reduced by glucocorticoids in adipose tissue from insulin-resistant rats.
abstract: OBJECTIVE
  Peripheral insulin resistance (IR) is one of the main side effects caused by glucocorticoid (GC)-based therapies, and the molecular mechanisms of GC-induced IR are not yet fully elucidated. Thus, we aimed to investigate the effects of dexamethasone treatment on the main components of insulin and inflammatory signaling in the adipose tissue of rats.
  
  
  METHODS
  Male Wistar rats received daily injections of dexamethasone (1mg/kg body weight (b.w.), intraperitoneally (i.p.)) for 5 days (DEX), whereas control rats received saline (CTL). The metabolic status was investigated, and the epididymal fat fragments were collected for lipolysis and western blot analyses.
  
  
  RESULTS
  The DEX rats became hyperglycemic, hyperinsulinemic, insulin resistant and glucose intolerant, compared with the CTL rats (P<0.05). The basal glycerol release in the fat fragments was 1.5-fold higher in the DEX rats (P<0.05). The phosphorylation of protein kinase B (PKB) at ser(473) decreased by 44%, whereas, the phosphorylation of insulin receptor substrate (IRS)-1 at ser(307) increased by 93% in the adipose tissue of the DEX rats after an oral bolus of glucose (P<0.05). The basal phosphorylation of c-jun-N-terminal kinase (JNK) and inhibitor of nuclear factor kappa-B (IKKβ) proteins was reduced by 46% and 58%, respectively, in the adipose tissue of the DEX rats (P<0.05). This was paralleled with a significant reduction (47%) in the glucocorticoid receptor (GR) protein content in the adipose tissue of the DEX rats (P<0.05).
  
  
  CONCLUSIONS
  The insulin-resistant status of rats induced by dexamethasone administration have PKB and IRS-1 activity attenuated in epididymal fat without increases in the phosphorylation of the proinflammatory signals JNK and IKKβ.
authors.affiliation: Multicenter Graduate Program in Physiological Sciences, Center of Biological Sciences, Federal University of Santa Catarina (UFSC), Florianópolis, Brazil.
authors.forename: Katia
authors.initials: K
authors.lastname: Motta
authors.affiliation: Graduate Program in Nutrition, Center of Health Sciences, Federal University of Santa Catarina (UFSC), Florianópolis, Brazil.
authors.forename: Amanda Marreiro
authors.initials: AM
authors.lastname: Barbosa
authors.affiliation: Graduate Program in Neurosciences, Center of Biological Sciences, Federal University of Santa Catarina (UFSC), Florianópolis, Brazil.
authors.forename: Franciane
authors.initials: F
authors.lastname: Bobinski
authors.affiliation: Graduate Program in Functional and Molecular Biology, Institute of Biology, Campinas State University (UNICAMP), Campinas, Brazil.
authors.forename: Antonio Carlos
authors.initials: AC
authors.lastname: Boschero
authors.affiliation: Multicenter Graduate Program in Physiological Sciences, Center of Biological Sciences, Federal University of Santa Catarina (UFSC), Florianópolis, Brazil. Electronic address: alex.rafacho@ufsc.br.
authors.forename: Alex
authors.initials: A
authors.lastname: Rafacho
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D001835:Body Weight; D016207:Cytokines / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D004822:Epididymis / Q000378:metabolism; D005938:Glucocorticoids / Q000378:metabolism*; D006003:Glycogen / Q000378:metabolism; D051550:I-kappa B Kinase / Q000378:metabolism*; D007249:Inflammation; D007328:Insulin / Q000378:metabolism; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D007333:Insulin Resistance; D048670:MAP Kinase Kinase 4 / Q000378:metabolism*; D008297:Male; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019289:Pyruvic Acid / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: D016207:Cytokines; D005938:Glucocorticoids; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D003907:Dexamethasone; D019289:Pyruvic Acid; D006003:Glycogen; D051057:Proto-Oncogene Proteins c-akt; D051550:I-kappa B Kinase; D048670:MAP Kinase Kinase 4
keywords: Dexamethasone; Glucocorticoid; Glucocorticoid receptor; Inflammatory signaling; Insulin resistance; Insulin signaling