title: Tumor necrosis factor alpha abolished the suppressive effect of insulin on hepatic glucose production and glycogenolysis stimulated by cAMP.
abstract: BACKGROUND
  Tumor necrosis factor alpha (TNFα) is implicated in the development of insulin resistance in obesity, type 2 diabetes and cancer. However, its ability to modulate the action of insulin on glycogen catabolism in the liver is controversial. The aim of the present study was to investigate whether TNFα acutely affects the suppression by insulin of hepatic glucose production (HGP) and glycogenolysis stimulated by cyclic adenosine monophosphate (cAMP).
  
  
  METHODS
  TNFα (10 μg/kg) was injected intravenously to rats and, 1 or 6h later, their livers were subjected to in situ perfusion with cAMP (3 μM), in the presence or absence of physiological (20 μU/mL) or supraphysiological (500 μU/mL) concentrations of insulin.
  
  
  RESULTS
  The injection of TNFα, 1 or 6h before liver perfusion, had no direct effect on the action of cAMP in stimulating HGP and glycogenolysis. However, when TNFα was injected 1h, but not 6h, before liver perfusion it completely abolished (p<0.05) the suppressive effect of 20 μU/mL insulin on HGP and glycogenolysis stimulated by cAMP. Furthermore, the injection of TNFα 1h or 6h before liver perfusion did not influence the suppression of cAMP-stimulated HGP and glycogenolysis by 500 μU/mL insulin.
  
  
  CONCLUSIONS
  TNFα acutely abolished the suppressive effect of physiological, but not supraphysiological, levels of insulin on HGP and glycogenolysis stimulated by cAMP, suggesting an important role of this mechanism to the increased HGP in several pathological states.
authors.affiliation: Department of Physiological Sciences, State University of Londrina, Londrina, PR, Brazil.
authors.forename: Aline Franco
authors.initials: AF
authors.lastname: da Rocha
authors.affiliation: Department of Physiological Sciences, State University of Londrina, Londrina, PR, Brazil.
authors.forename: Thaís Fernanda
authors.initials: TF
authors.lastname: Liboni
authors.affiliation: Department of Physiological Sciences, State University of Londrina, Londrina, PR, Brazil.
authors.forename: Mirian Ayumi
authors.initials: MA
authors.lastname: Kurauti
authors.affiliation: Department of Physiological Sciences, State University of Londrina, Londrina, PR, Brazil.
authors.forename: Camila Oliveira
authors.initials: CO
authors.lastname: de Souza
authors.affiliation: Department of Physiological Sciences, State University of Londrina, Londrina, PR, Brazil.
authors.forename: Daniele Romani
authors.initials: DR
authors.lastname: Miksza
authors.affiliation: Department of Physiological Sciences, State University of Londrina, Londrina, PR, Brazil.
authors.forename: Carolina Campos Lima
authors.initials: CC
authors.lastname: Moreira
authors.affiliation: Department of Physiological Sciences, State University of Londrina, Londrina, PR, Brazil.
authors.forename: Glaucia Regina
authors.initials: GR
authors.lastname: Borba-Murad
authors.affiliation: Department of Pharmacology and Therapeutics, State University of Maringá, Maringá, PR, Brazil.
authors.forename: Roberto Barbosa
authors.initials: RB
authors.lastname: Bazotte
authors.affiliation: Department of Physiological Sciences, State University of Londrina, Londrina, PR, Brazil. Electronic address: hmedri@uel.br.
authors.forename: Helenir Medri
authors.initials: HM
authors.lastname: de Souza
mesh_terms: D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D050261:Glycogenolysis / Q000502:physiology*; D007328:Insulin / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008112:Liver Glycogen / Q000378:metabolism; D008297:Male; D010477:Perfusion / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D007328:Insulin; D008112:Liver Glycogen; D014409:Tumor Necrosis Factor-alpha; D000242:Cyclic AMP; D005947:Glucose
keywords: Cyclic AMP; Glycogenolysis; Hepatic glucose production; Insulin resistance; TNFα