Journal
CELLS
Volume 10, Issue 1, Pages -Publisher
MDPI
DOI: 10.3390/cells10010099
Keywords
estradiol; phytoestrogens; ESR1; ESR2; GLUT4; glycemic homeostasis; diabetes mellitus
Categories
Funding
- Sao Paulo State Foundation for Research (FAPESP) [2008/51094-7, 02/07384-4, 2012/04831-1, 2017/194499]
- Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior-Brasil (CAPES) [88887.355005/2019-00]
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) [140362/2020-7]
Ask authors/readers for more resources
This study reviews the relationship between estrogen and diabetes mellitus, focusing on glycemic homeostasis, estrogen, ESR1/ESR2, and GLUT4. The research findings suggest that ESR1-mediated effects are beneficial while ESR2-mediated effects are detrimental to glycemic homeostasis.
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 Esr1(-/-) and Esr2(-/-) transgenic mice. We specifically address estradiol-induced and ESR1/ESR2-mediated regulation of the solute carrier family 2 member 4 (Slc2a4) gene, examining ESR1/ESR2-mediated genomic mechanisms that regulate Slc2a4 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available