2-methoxyoestradiol inhibits glucose transport in rodent skeletal muscle: Experimental physiology

Abstract

2-Methoxyoestradiol (2-ME) is an oestrogen derivative that inhibits superoxide dismutase (which converts superoxide anions to H2O 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-[1,2-3H]glucose. 2-Methoxyoestradiol (50 μm) reduced glucose uptake induced by insulin, contraction and hypoxia by ∼60%. Exogenous H2O2 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 (∼60%). Moreover, basal glucose uptake was decreased by 2-ME (∼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. © 2010 The Physiological Society.