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GLUT4 gene regulation by estrogen: role of receptors ER alfa and ER beta

Grant number: 09/02217-1
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): May 01, 2009
Effective date (End): December 31, 2012
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal Investigator:Ubiratan Fabres Machado
Grantee:Raquel Saldanha Campello
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:07/50554-1 - Glucose transporters and diabetes mellitus: contribution to the knowledge of glycemic control and chronic diseases development, AP.TEM

Abstract

Insulin resistance results from a combination of genetic and environmental factors and may be considered the primary cause for the development of metabolic disorders, such as type 2 diabetes mellitus (DM). It is characterized by a reduced ability of the insulin sensitive tissues to respond to normal levels of the hormone. In these tissues, glucose transport stimulated by insulin occurs through the glucose transporter (GLUT4) and alterations in its genic expression are related to changes in insulin sensitivity. It is known estradiol (E2) modulates insulin sensitivity and previous studies from our group revealed it also participates in the GLUT4 gene regulation. The present project is aimed at investigating the GLUT4 gene regulation by E2 in vitro, as welll as the mechanisms involved in this regulation. 3T3-L1 adipose cells will be treated with 17² Estradiol for different times (1, 2, 4 e 6 days) and at different concentrations (0.1, 1, 10 e 100 nM), for evaluation of GLUT4 mRNA and protein contents. Once the conditions of higher E2 effect are determined, the cells will be additionally treated with selective agonists and antagonists for E2 recptors (ER-a e ER-b). In addition, the interaction and binding of ERs and NFkB to the GLUT4 gene promoter will be investigated. With this study, we intend to demonstrate the importance of the estrogens in the GLUT4 gene regulation, unveiling the molecular mechanisms involved and defining the estrogens biologic role in the glycemic control of both female and male. Moreover, we believe this study will be able to contribute to the development of new preventive/ therapeutic strategies for the treatment of DM. (AU)

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
CAMPELLO, R. S.; ALVES-WAGNER, A. B.; LUCAS, T. F.; MORI, R. C.; FURUYA, D. T.; PORTO, C. S.; MACHADO, U. F. Estrogen Receptor 1 Agonist PPT Stimulates Slc2a4 Gene Expression and Improves Insulin-Induced Glucose Uptake in Adipocytes. CURRENT TOPICS IN MEDICINAL CHEMISTRY, v. 12, n. 19, p. 2059-2069, OCT 2012. Web of Science Citations: 12.
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
CAMPELLO, Raquel Saldanha. 17b-estradiol aumenta a expressão de Slc2a4/GLUT4 em adipócitos 3T3-L1 via ESR1.. 2012. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas São Paulo.

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