REGULATION OF Slc2a4/GLUT4 EXPRESSION BY 17²-ESTRADIOL

• Grant number: 12/24210-1
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Effective date (Start): March 01, 2013
• Effective date (End): August 27, 2016
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Ubiratan Fabres Machado
• Grantee: Raquel Saldanha Campello
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 12/04831-1 - New players in glycemic control and chronic complications of Diabetes mellitus: preventive and therapeutic perspectives, AP.TEM
• Associated scholarship(s): 14/00992-6 - Regulation of SLC2A4 expression by 17b estradiol: effects of estrogen receptors interaction with PPARgamma and NF-kB, BE.EP.PD

Abstract

Insulin resistance (IR) occurs from a combination of genetic and environmental factors and is considered the primary cause for the development of type 2 diabetes mellitus (DM). It manifests as a reduced capacity of insulin sensitive tissues respond to normal levels of the hormone. In these tissues, glucose transportation in response to insulin occurs through GLUT4 (SLC2a4gene) and changes in the translocation to the membrane and/or gene expression of this carrier are related with IR. It is known that estradiol (E2) is involved in the modulation of insulin sensitivity, and previous studies of our group showed that the E2 participates in the regulation of the SLC2A4/GLUT4 expression; however, its exact genomic mechanism has not been fully clarified. In addition, the non-genomic effects of E2 on the SLC2a4 expression and/or GLUT4translocation have never been investigated. The present project aims to investigate the effect of E2 and the molecular mechanisms involved in the regulation of the SLC2a4 expression and GLUT4translocation. Adipocytes 3T3-L1 will be treated for 1 day with 17² Estradiol for the assessment of the change in the expression of the miRNAs involved in GLUT4 regulation. Additionally, they will be treated with selective agonists and antagonists for the E2 receptors (ESR1, ESR2 and GPER) for the evaluation of nuclear transactivation and/or extra nuclear activation of NFkB, and the analysis of intracellular signaling pathways and their effects on glucose homeostasis. The results are expected to elucidate the molecular mechanisms involved in the SLC2A4/GLUT4 regulation by E2 as well as define its biological action in glycemic control, and thus contribute to the knowledge of new preventive and/or therapeutic strategies for DM treatment.

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)

FATIMA, LUCIANA A.; CAMPELLO, RAQUEL S.; BARRETO-ANDRADE, JOAO N.; PASSARELLI, MARISA; SANTOS, ROBERTA S.; CLEGG, DEBORAH J.; MACHADO, UBIRATAN F.. Estradiol stimulates adipogenesis and Slc2a4/GLUT4 expression via ESR1-mediated activation of CEBPA. Molecular and Cellular Endocrinology, v. 498, DEC 1 2019. (16/15603-0, 12/24210-1)

CAMPELLO, RAQUEL S.; FATIMA, LUCIANA A.; BARRETO-ANDRADE, JOAO NILTON; LUCAS, THAIS F.; MORI, ROSANA C.; PORTO, CATARINA S.; MACHADO, UBIRATAN F.. Estradiol-induced regulation of GLUT4 in 3T3-L1 cells: involvement of ESR1 and AKT activation. JOURNAL OF MOLECULAR ENDOCRINOLOGY, v. 59, n. 3, p. 257-268, OCT 2017. (12/04831-1, 12/24210-1)