tailieunhanh - Báo cáo khoa học: 1. Signal Transduction 1.1 Integration of Metabolism and Survival

Estrogen is known to influence glucose homeostasis but the role of estrogen receptors in muscle glucose metabolism is unknown. Therefore, we investigated the expression of the two estrogen receptors, ERa and ERb and their influence on regulation of GLUT4, and its associated structural protein, caveolin-1, in mouse muscle. ERaand ERbare co-expressed in the nuclei of most muscle cells and their levels were not affected by absence of estradiol (in aromatase knockout, ArKO, mice). | Abstracts 1. Signal Transduction Integration of Metabolism and Survival 1 Regulation of metabolism by estrogen signaling J. Gustafsson R. Rodrigo and W. Warner Department of BioSciences and Nutrition Novum Karolinska Institutet Stockholm Sweden. E-mail Estrogen is known to influence glucose homeostasis but the role of estrogen receptors in muscle glucose metabolism is unknown. Therefore we investigated the expression of the two estrogen receptors ERa and ERb and their influence on regulation of GLUT4 and its associated structural protein caveolin-1 in mouse muscle. ERa and ERb are co-expressed in the nuclei of most muscle cells and 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 ERb but was extremely reduced in ER a mice and elevated in ArKO mice. Upon treatment of ArKO mice with the ERb agonist DPN GLUT4 expression was reduced. Caveolin-1 expression was higher in ArKO mice and lower in ERb and ERa mice than in WT littermates. GLUT4 and caveolin-1 were colocalized in WT and ArKO mice but not in ERb and ERa mice. Thus ERa is necessary for GLUT4 expression while ERb has a suppressive role. Both ERb and ERa are necessary for optimal caveolin-1 expression. Taken together these results indicate that reduction in GLUT4 is a plausible explanation for the insulin resistance observed in ERa mice and that colocalization of caveolin-1 and GLUT4 is not an absolute requirement for muscle glucose metabolism. 2 Nutritional sensing in the MTOR S6K1 pathway in the development of obesity and diabetes G. Thomas Genome Science Genome Reserach Institute Cincinnati OH USA. E-mail thomasg4@ Earlier we showed that nutrient overload induces S6K1 activation which suppresses insulin-induced class 1 PI3K signaling leading to insulin resistance. Counter to the prevailing view our recent studies show that the nutrient . amino