title: The flavonoid silibinin decreases glucose-6-phosphate hydrolysis in perfused rat hepatocytes by an inhibitory effect on glucose-6-phosphatase.
abstract: OBJECTIVE
  The flavonoid silibinin has been reported to be beneficial in several hepatic disorders. Recent evidence also suggests that silibinin could be beneficial in the treatment of type 2 diabetes, owing to its anti-hyperglycemic properties. However, the mechanism(s) underlying these metabolic effects remains unknown.
  
  
  METHODS
  The effects of silibinin on liver gluconeogenesis were studied by titrating hepatocytes from starved rats with sub-saturating concentrations of various exogenous substrates in a perifusion system. Hepatocytes from fed rats were also used to investigate glycogenolysis from endogenous glycogen. The effect of silibinin on glucose-6-phosphatase kinetics was determined in intact and permeabilized rat liver microsomes.
  
  
  RESULTS
  Silibinin induced a dose-dependent inhibition of gluconeogenesis associated with a potent decrease in glucose-6-phosphate hydrolysis. This effect was demonstrated whatever the gluconeogenic substrates used, i.e. dihydroxyacetone, lactate/pyruvate, glycerol and fructose. In addition, silibinin decreased the glucagon-induced stimulation of both gluconeogenesis and glycogenolysis, this being associated with a reduction of glucose-6-phosphate hydrolysis. Silibinin inhibits glucose-6-phosphatase in rat liver microsomes in a concentration-dependent manner that could explain the decrease in glucose-6-phosphate hydrolysis seen in intact cells.
  
  
  CONCLUSIONS
  The inhibitory effect of silibinin on both hepatic glucose-6-phosphatase and gluconeogenesis suggests that its use may be interesting in treatment of type 2 diabetes.
authors.affiliation: Departamento de Fisiologia y Farmacologia, Facultad de Farmacia, Universidad de Salamanca, Campus Miguel de Unamuno, Salamanca, Spain [corrected].
authors.forename: Bruno
authors.initials: B
authors.lastname: Guigas
authors.forename: Roula
authors.initials: R
authors.lastname: Naboulsi
authors.forename: Gloria R
authors.initials: GR
authors.lastname: Villanueva
authors.forename: Nellie
authors.initials: N
authors.lastname: Taleux
authors.forename: José M
authors.initials: JM
authors.lastname: Lopez-Novoa
authors.forename: Xavier M
authors.initials: XM
authors.lastname: Leverve
authors.forename: Mohamad-Yehia
authors.initials: MY
authors.lastname: El-Mir
mesh_terms: D000818:Animals; D004098:Dihydroxyacetone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000494:pharmacology*; D005934:Glucagon / Q000494:pharmacology; D005943:Gluconeogenesis / Q000187:drug effects; D005952:Glucose-6-Phosphatase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019298:Glucose-6-Phosphate / Q000378:metabolism*; D006019:Glycolysis / Q000187:drug effects; D022781:Hepatocytes / Q000187:drug effects* / Q000201:enzymology*; D006868:Hydrolysis / Q000187:drug effects; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D010477:Perfusion; D010539:Permeability / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D000077385:Silybin; D012838:Silymarin / Q000494:pharmacology
chemical_list: D005419:Flavonoids; D012838:Silymarin; D000077385:Silybin; D019298:Glucose-6-Phosphate; D005934:Glucagon; D005952:Glucose-6-Phosphatase; D004098:Dihydroxyacetone