Muscle GLUT4 regulation by estrogen receptors ERbeta and ERalpha.

@article{citeulike:2241750, abstract = {Estrogen is known to influence glucose homeostasis with dominant effects in the liver, but the role of estrogen receptors in muscle glucose metabolism is unknown. In the present study, we investigated the expression of the two estrogen receptors, ERalpha and ERbeta, and their influence on regulation of the glucose transporter, GLUT4, and its associated structural protein, caveolin-1, in mouse gastrocnemius muscle. Immunohistochemical analysis revealed that ERalpha and ERbeta are coexpressed in the nuclei of most muscle cells, and that their levels were not affected by absence of estradiol [in aromatase-knockout (ArKO) mice]. GLUT4 expression on the muscle cell membrane was not affected by loss of ERbeta but was extremely reduced in ERalpha(-/-) mice and elevated in ArKO mice. RT-PCR confirmed a parallel reduction in GLUT4 mRNA levels in ERalpha(-/-) mice. Upon treatment of ArKO mice with the ERbeta agonist 2,3-bis(4-hydroxyphenyl)propionitrile, GLUT4 expression was reduced. By immunofluorescence and Western blotting, caveolin-1 expression was higher in ArKO mice and lower in ERbeta(-/-) and ERalpha(-/-) mice than in WT littermates. GLUT4 and caveolin-1 were colocalized in WT and ArKO mice but not in ERbeta(-/-) and ERalpha(-/-) mice. These results reveal that ERalpha is a positive regulator of GLUT4 expression, whereas ERbeta has a suppressive role. Both ERbeta and ERalpha are necessary for optimal caveolin-1 expression. Taken together, these results indicate that colocalization of caveolin-1 and GLUT4 is not an absolute requirement for muscle glucose metabolism but that reduction in GLUT4 could be contributing to the insulin resistance observed in ERalpha(-/-) mice.}, address = {Department of Biosciences and Nutrition, Karolinska Institute, S-141 86 Novum, Sweden.}, author = {Barros, R. P. and Machado, U. F. and Warner, M. and Gustafsson, J. A. }, citeulike-article-id = {2241750}, doi = {10.1073/pnas.0510391103}, issn = {0027-8424}, journal = {Proc Natl Acad Sci U S A}, keywords = {alpha, arko, beta, erko, estrogen, glut4, mouse, receptor}, month = {January}, number = {5}, pages = {1605--1608}, posted-at = {2008-01-16 22:36:27}, priority = {2}, title = {Muscle GLUT4 regulation by estrogen receptors ERbeta and ERalpha.}, url = {http://dx.doi.org/10.1073/pnas.0510391103}, volume = {103}, year = {2006} }

TY - JOUR ID - citeulike:2241750 L3 - citeulike-article-id:2241750 TI - Muscle GLUT4 regulation by estrogen receptors ERbeta and ERalpha. JF - Proc Natl Acad Sci U S A VL - 103 IS - 5 SP - 1605 EP - 1608 AD - Department of Biosciences and Nutrition, Karolinska Institute, S-141 86 Novum, Sweden. SN - 0027-8424 N2 - Estrogen is known to influence glucose homeostasis with dominant effects in the liver, but the role of estrogen receptors in muscle glucose metabolism is unknown. In the present study, we investigated the expression of the two estrogen receptors, ERalpha and ERbeta, and their influence on regulation of the glucose transporter, GLUT4, and its associated structural protein, caveolin-1, in mouse gastrocnemius muscle. Immunohistochemical analysis revealed that ERalpha and ERbeta are coexpressed in the nuclei of most muscle cells, and that their levels were not affected by absence of estradiol [in aromatase-knockout (ArKO) mice]. GLUT4 expression on the muscle cell membrane was not affected by loss of ERbeta but was extremely reduced in ERalpha(-/-) mice and elevated in ArKO mice. RT-PCR confirmed a parallel reduction in GLUT4 mRNA levels in ERalpha(-/-) mice. Upon treatment of ArKO mice with the ERbeta agonist 2,3-bis(4-hydroxyphenyl)propionitrile, GLUT4 expression was reduced. By immunofluorescence and Western blotting, caveolin-1 expression was higher in ArKO mice and lower in ERbeta(-/-) and ERalpha(-/-) mice than in WT littermates. GLUT4 and caveolin-1 were colocalized in WT and ArKO mice but not in ERbeta(-/-) and ERalpha(-/-) mice. These results reveal that ERalpha is a positive regulator of GLUT4 expression, whereas ERbeta has a suppressive role. Both ERbeta and ERalpha are necessary for optimal caveolin-1 expression. Taken together, these results indicate that colocalization of caveolin-1 and GLUT4 is not an absolute requirement for muscle glucose metabolism but that reduction in GLUT4 could be contributing to the insulin resistance observed in ERalpha(-/-) mice. KW - alpha KW - arko KW - beta KW - erko KW - estrogen KW - glut4 KW - mouse KW - receptor AU - Barros, RP AU - Machado, UF AU - Warner, M AU - Gustafsson, JA PY - 2006/01/31/ UR - http://dx.doi.org/10.1073/pnas.0510391103 ER -