Estrogen and Glycemic Homeostasis: The Fundamental Role of Nuclear Estrogen Receptors ESR1/ESR2 in Glucose Transporter GLUT4 Regulation

Impaired circulating estrogen levels have been related to impaired glycemic homeostasis and diabetes mellitus (DM), both in females and males. However, for the last twenty years, the relationship between estrogen, glycemic homeostasis and the mechanisms involved has remained unclear. The characteriz...

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Published inCells (Basel, Switzerland) Vol. 10; no. 1; p. 99
Main Authors Gregorio, Karen Cristina Rego, Laurindo, Caroline Pancera, Machado, Ubiratan Fabres
Format Journal Article
LanguageEnglish
Published Switzerland MDPI AG 07.01.2021
MDPI
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Summary:Impaired circulating estrogen levels have been related to impaired glycemic homeostasis and diabetes mellitus (DM), both in females and males. However, for the last twenty years, the relationship between estrogen, glycemic homeostasis and the mechanisms involved has remained unclear. The characterization of estrogen receptors 1 and 2 (ESR1 and ESR2) and of insulin-sensitive glucose transporter type 4 (GLUT4) finally offered a great opportunity to shed some light on estrogen regulation of glycemic homeostasis. In this manuscript, we review the relationship between estrogen and DM, focusing on glycemic homeostasis, estrogen, ESR1/ESR2 and GLUT4. We review glycemic homeostasis and GLUT4 expression (muscle and adipose tissues) in and transgenic mice. We specifically address estradiol-induced and ESR1/ESR2-mediated regulation of the 4 ( ) gene, examining ESR1/ESR2-mediated genomic mechanisms that regulate transcription, especially those occurring in cooperation with other transcription factors. In addition, we address the estradiol-induced translocation of ESR1 and GLUT4 to the plasma membrane. Studies make it clear that ESR1-mediated effects are beneficial, whereas ESR2-mediated effects are detrimental to glycemic homeostasis. Thus, imbalance of the ESR1/ESR2 ratio may have important consequences in metabolism, highlighting that ESR2 hyperactivity assumes a diabetogenic role.
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These authors contributed equally to this work.
ISSN:2073-4409
2073-4409
DOI:10.3390/cells10010099