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.
Zhang
Shi-Jin
SJ
Karolinska Institutet, Department of Physiology and Pharmacology, Stockholm, Sweden.
Sandström
Marie
M
Ahlsén
Maria
M
Ivarsson
Niklas
N
Zhu
Hua
H
Ma
Jianjie
J
Ren
Jian-Ming
JM
Westerblad
Håkan
H
Katz
Abram
A
D000077584:2-Methoxyestradiol; D000818:Animals; D003847:Deoxyglucose / Q000378:metabolism; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology; D000860:Hypoxia / Q000503:physiopathology; D007328:Insulin / Q000494:pharmacology; D008297:Male; D051379:Mice; D009119:Muscle Contraction; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D051381:Rats
D051275:Glucose Transporter Type 4; D007328:Insulin; D004958:Estradiol; D000077584:2-Methoxyestradiol; D003847:Deoxyglucose; D006861:Hydrogen Peroxide; D005947:Glucose