The flavonoid silibinin decreases glucose-6-phosphate hydrolysis in perfused rat hepatocytes by an inhibitory effect on glucose-6-phosphatase.

Guigas, Bruno;Naboulsi, Roula;Villanueva, Gloria R.;Taleux, Nellie;El-Mir, Mohamad-Yehia;et.al.
(2007) Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology — Vol. 20, n° 6, p. 925-934 (2007)

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  • Guigas, BrunoUCLouvain
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  • Naboulsi, Roula
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  • Villanueva, Gloria R.
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  • Taleux, NellieUCLouvain
    Author
  • El-Mir, Mohamad-Yehia
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Abstract
BACKGROUND/AIMS: 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. CONCLUSION: 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.
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Guigas, B., Naboulsi, R., Villanueva, G. R., Taleux, N., Lopez-Novoa, J. E. M., Leverve, X. M., & El-Mir, M.-Y. (2007). The flavonoid silibinin decreases glucose-6-phosphate hydrolysis in perfused rat hepatocytes by an inhibitory effect on glucose-6-phosphatase. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology, 20(6), 925-934. https://doi.org/10.1159/000110453 (Original work published 2007)