AP, Glut4, Estrogen, someone decipher this please

  1. AP, Glut4, Estrogen, someone decipher this please

    Muscle GLUT4 regulation by estrogen receptors ERβ and ERα

    And in english this says what????

    Looks to me like activation of certain estrogen receptors is good for glut4 while activation of other receptors is bad.


  2. To quote myself many moons ago-

    Quote Originally Posted by Ziricote
    Abstract and Full Article from PubMed Central- Muscle GLUT4 regulation by estrogen receptors ER1 and ER2
    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, ER1 and ER2, 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 ER1 and ER2 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 ER2 but was extremely reduced in ER1-/- mice and elevated in ArKO mice. RT-PCR confirmed a parallel reduction in GLUT4 mRNA levels in ER1-/- mice. Upon treatment of ArKO mice with the ER2 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 ER2-/- and ER1-/- mice than in WT littermates. GLUT4 and caveolin-1 were colocalized in WT and ArKO mice but not in ER2-/- and ER1-/- mice. These results reveal that ER1 is a positive regulator of GLUT4 expression, whereas ER2 has a suppressive role. Both ER2 and ER1 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 ER1-/- mice.
    -Absence of Estradiol does not effect either Estrogen Receptors
    -Low ER2 activity does not effect GLUT4 expression in muscle
    -Low ER1 activity (e.g. via AI) extremely reduces GLUT4 expression in muscle
    -Both ER1 & 2 are necessary for optimal Caveolin-1
    -Neither GLUT4 or Caveolin-1 are necessary for muscle glucose metabolism
    -Absence of GLUT4 in muscle could contribute to Insulin resistance and it's associated health problems
    There's no "One receptor is bad" because while ER-Alpha/1 regulates GLUT4 in muscle, ER-Beta/2 has been said to regulate ER-Alpha to an extent. The only thing I can take from this study is that potent Aromatase Inhibitors like Exemestane can reduce GLUT4 via low ER-Alpha activity, fact of the matter is that you would have to seriously lower Oestrogens and there simply is no reason for healthy individuals to do so in the real world.

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