2-Methoxyoestradiol inhibits glucose transport in rodent skeletal muscle

2-Methoxyoestradiol (2-ME) is an oestrogen derivative that inhibits superoxide dismutase (which converts superoxide anions to H(2)O(2)). Since reactive oxygen species have been implicated in glucose transport, we determined the effect of 2-ME on glucose transport in skeletal muscle. Experiments were performed on isolated mouse extensor digitorum longus (EDL, glycolytic, fast-twitch) muscle. Glucose uptake was measured using 2-deoxy-d-[1,2-(3)H]glucose. 2-Methoxyoestradiol (50 microm) reduced glucose uptake induced by insulin, contraction and hypoxia by approximately 60%. Exogenous H(2)O(2) activated glucose uptake, and this effect was also blocked by 2-ME, demonstrating that 2-ME was exerting its inhibitory effect on glucose uptake at a site other than superoxide dismutase. When glucose uptake was stimulated by insulin, followed by addition of 2-ME, there was also an attenuation of the effect of insulin (approximately 60%). Moreover, basal glucose uptake was decreased by 2-ME (approximately 50%). In contrast, insulin-mediated translocation of glucose transporter type 4 protein to the plasma membrane was not affected by 2-ME. Similar results were obtained in soleus (oxidative, slow-twitch) muscle. In conclusion, 2-ME appears to decrease glucose transport in skeletal muscle by directly interfering with the function of glucose transport proteins in surface membranes.