BACKGROUND: Silybin (SB) is the main flavonolignan of silymarin used for its hepatoprotective effects in human medicine (Legalon). Our group have previously reported that SB has antidiabetic effects at least by inhibiting hepatic gluconeogenesis in perifused liver cells (Naboulsi et al, Doctoral Thesis, 2006). AIM: Investigate the antiglucagon effect of silybin as a possible mechanism by which SB exerts its antidiabetic effects.

METHODS: We studied the effect of silybin (100 mM) on liver gluconeogenesis by titrating isolated hepatocytes from 24h starved rats with sub-saturating concentrations of exogenous substrates (dihydroxyacetone, lactate/pyruvate, glycerol and fructose) in a cell perifusion system in the presence or absence of glucagon 0.1 mM. Also we investigated the effect of SB (100 mM) on hepatic glycogenolysis in perifused fed rat liver cells.

RESULTS: Silibyn induced a dose-dependent inhibition of gluconeogenesis associated with a potent decrease in glucose-6-phosphate hydrolysis in the presence of various substrates: dihydroxyacetone (DHA), lactate/pyruvate, glycerol and fructose. Silybin also decreased the glucagon-induced stimulation of gluconeogenesis from DHA. In addition, the flavonoid attenuated the glucagon-induced stimulation of glycogenolysis and reduced glucose-6-phosphate hydrolysis in hepatocytes from fed rats. Finally, we showed that SB exerts a direct inhibition of glucose-6-phosphatase activity.

CONCLUSION: Silybin exerts its antidiabetic effects, at least, by antogonizing the well known metabolic effects of glucagon on hepatic gluconeogenesis and glicogenolysis. This antiglucagon effect of SB is mediated by inhibition of the hepatic glucose-6-phosphatase activity. These results suggest that the use of silybin may be interesting in the treatment of type 2 diabetes.