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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| Format: | Article |
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MDPI AG
2021-01-01
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| Online Access: | https://www.mdpi.com/2073-4409/10/1/99 |
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| author | Karen Cristina Rego Gregorio Caroline Pancera Laurindo Ubiratan Fabres Machado |
| author_facet | Karen Cristina Rego Gregorio Caroline Pancera Laurindo Ubiratan Fabres Machado |
| author_sort | Karen Cristina Rego Gregorio |
| collection | DOAJ |
| description | 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 <i>Esr1</i><sup>−/−</sup> and <i>Esr2</i><sup>−/−</sup> transgenic mice. We specifically address estradiol-induced and ESR1/ESR2-mediated regulation of the <i>solute carrier family 2 member</i> 4 (<i>Slc2a4</i>) gene, examining ESR1/ESR2-mediated genomic mechanisms that regulate <i>Slc2a4</i> 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. |
| first_indexed | 2024-03-09T05:42:20Z |
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| id | doaj.art-99bb119aee8843f4ae06a9e3d1bd1de1 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T05:42:20Z |
| publishDate | 2021-01-01 |
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| series | Cells |
| spelling | doaj.art-99bb119aee8843f4ae06a9e3d1bd1de12023-12-03T12:23:52ZengMDPI AGCells2073-44092021-01-011019910.3390/cells10010099Estrogen and Glycemic Homeostasis: The Fundamental Role of Nuclear Estrogen Receptors ESR1/ESR2 in Glucose Transporter GLUT4 RegulationKaren Cristina Rego Gregorio0Caroline Pancera Laurindo1Ubiratan Fabres Machado2Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes 1524, São Paulo (SP) 05508-900, BrazilDepartment of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes 1524, São Paulo (SP) 05508-900, BrazilDepartment of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes 1524, São Paulo (SP) 05508-900, BrazilImpaired 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 <i>Esr1</i><sup>−/−</sup> and <i>Esr2</i><sup>−/−</sup> transgenic mice. We specifically address estradiol-induced and ESR1/ESR2-mediated regulation of the <i>solute carrier family 2 member</i> 4 (<i>Slc2a4</i>) gene, examining ESR1/ESR2-mediated genomic mechanisms that regulate <i>Slc2a4</i> 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.https://www.mdpi.com/2073-4409/10/1/99estradiolphytoestrogensESR1ESR2GLUT4glycemic homeostasis |
| spellingShingle | Karen Cristina Rego Gregorio Caroline Pancera Laurindo Ubiratan Fabres Machado Estrogen and Glycemic Homeostasis: The Fundamental Role of Nuclear Estrogen Receptors ESR1/ESR2 in Glucose Transporter GLUT4 Regulation Cells estradiol phytoestrogens ESR1 ESR2 GLUT4 glycemic homeostasis |
| title | Estrogen and Glycemic Homeostasis: The Fundamental Role of Nuclear Estrogen Receptors ESR1/ESR2 in Glucose Transporter GLUT4 Regulation |
| title_full | Estrogen and Glycemic Homeostasis: The Fundamental Role of Nuclear Estrogen Receptors ESR1/ESR2 in Glucose Transporter GLUT4 Regulation |
| title_fullStr | Estrogen and Glycemic Homeostasis: The Fundamental Role of Nuclear Estrogen Receptors ESR1/ESR2 in Glucose Transporter GLUT4 Regulation |
| title_full_unstemmed | Estrogen and Glycemic Homeostasis: The Fundamental Role of Nuclear Estrogen Receptors ESR1/ESR2 in Glucose Transporter GLUT4 Regulation |
| title_short | Estrogen and Glycemic Homeostasis: The Fundamental Role of Nuclear Estrogen Receptors ESR1/ESR2 in Glucose Transporter GLUT4 Regulation |
| title_sort | estrogen and glycemic homeostasis the fundamental role of nuclear estrogen receptors esr1 esr2 in glucose transporter glut4 regulation |
| topic | estradiol phytoestrogens ESR1 ESR2 GLUT4 glycemic homeostasis |
| url | https://www.mdpi.com/2073-4409/10/1/99 |
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