Genistein inhibits glucose and sulphate transport in isolated rat liver lysosomes

Abstract

Genistein and daidzein are known to have both beneficial and adverse effects on human health due to their many biological actions at the cellular level. Both isoflavones have been shown to inhibit GLUT-mediated glucose transport across the plasma membrane of mammalian cells. Since lysosomal membrane transport is essential for maintaining cellular homeostasis, the present study examined the effects of genistein and daidzein on glucose and sulphate transport in isolated rat liver lysosomes. Both genistein and daidzein significantly inhibited lysosomal glucose uptake. Genistein was a more potent glucose transport inhibitor than daidzein, with a half-maximum inhibitory concentration (IC50) of 45 μmol/l compared with 71 μmol/l for daidzein. Uptake kinetics ofd-glucose showed a significant decrease inVmax(control:genistein treat = 1489 (sem91):507 (sem76) pmol/unit of β-hexosaminidase per 15 s) without a change inKm. The presence of 50 μm-genistein in the medium also reduced glucose efflux from lysosomes preloaded with 100 mm-d-glucose. Genistein also inhibited lysosomal sulphate transport. Similar to its effects on glucose uptake kinetics, genistein treatment caused a significant decrease in sulphate uptakeVmax(control:genistein treat = 87 (sem4):59 (sem5) pmol/unit of β-hexosaminidase per 30 s), while theKmwas not affected. The evidence provided by the present study suggests that the most likely mechanism of lysosomal glucose transport inhibition by genistein is via direct interaction between genistein and the transporter, rather than mediation by tyrosine kinase inactivation. Genistein likely has a similar mechanism of directly inhibiting sulphate transporter.