Estrogen Receptor 1 Agonist PPT Stimulates Slc2a4 Gene Expression and Improves Insulin-Induced Glucose Uptake in Adipocytes

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dc.contributor.author Campello, R. S.
dc.contributor.author Alves-Wagner, A. B.
dc.contributor.author Lucas, T. F. [UNIFESP]
dc.contributor.author Mori, R. C.
dc.contributor.author Furuya, D. T.
dc.contributor.author Porto, Catarina Segreti [UNIFESP]
dc.contributor.author Machado, U. F.
dc.date.accessioned 2018-06-15T17:05:15Z
dc.date.available 2018-06-15T17:05:15Z
dc.date.issued 2012-10-01
dc.identifier http://dx.doi.org/10.2174/1568026611212190004
dc.identifier.citation Current Topics In Medicinal Chemistry. Sharjah: Bentham Science Publ Ltd, v. 12, n. 19, p. 2059-2069, 2012.
dc.identifier.issn 1568-0266
dc.identifier.uri http://repositorio.unifesp.br/11600/43475
dc.description.abstract Type 2 diabetes mellitus is characterized by disruption in glycemic homeostasis, involving impaired insulin-induced glucose disposal. For that, reduced glucose transporter GLUT4, encoded by Slc2a4 gene, plays a fundamental role. Conversely, increase in Slc2a4/GLUT4 expression improves glycemic homeostasis. Recent studies have proposed that estradiol is able to modulate Slc2a4 expression, according to distinct effects upon estrogen receptors ESR1/ESR2. We hypothesize that ESR1-agonist effect could stimulate Slc2a4 expression; thus, increasing cellular glucose disposal, which could be beneficial to glycemic control. Differentiated 3T3-L1 adipocytes were treated (24 hours) with selective ESR1-agonist PPT 1,3,5-tris(4-hydroxyphenyl)-4- propyl-1H-pyrazole, selective ESR1-antagonist MPP 1,3-Bis(4-hydroxyphenyl)-4- methyl-5-[4-(2-piperidinylethoxy)phenol]-1H-pyrazole dihydrochloride, and selective ESR2 agonist DPN 2,3-bis(4-Hydroxyphenyl)-propionitrile, with/without 17 beta-estradiol (E2). We analyzed Slc2a4 mRNA (real time PCR) and GLUT4 protein (Western blotting) expression, transcriptional activity of the Slc2a4 repressor Nuclear Factor-kappa B (NF-kappa B) (electrophoretic mobility shift assay), and cellular glucose disposal (2-deoxi-D-[H-3]glucose uptake, 2-DG). ESR1-agonist PPT enhanced Slc2a4/GLUT4 expression (similar to 30%) in the absence or presence of 0.1 and 10 nmol/L E2, and decreased the NF-kappa B binding activity (similar to 50%). Conversely, ESR1-antagonist MPP, together with E2, decreased Slc2a4/GLUT4 expression (20-40%) and increased NF-kappa B binding activity (similar to 30%). Furthermore, treatment with ESR2-agonist DPN decreased Slc2a4/GLUT4 expression (20-50%). 2-DG uptake was modulated in parallel to that observed in GLUT4 protein. The present results reveal that ESR1 activity enhances, whereas ESR2 activity represses, Slc2a4/GLUT4 expression. These effects are partially mediated by NF-kappa B, and allow parallel changes in adipocyte glucose disposal. Furthermore, the data provide evidences that ESR1-agonist PPT, as a Slc2a4/GLUT4 enhancer, can be a promising coadjuvant d(r)ug for diabetes mellitus therapy. en
dc.description.sponsorship Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.format.extent 2059-2069
dc.language.iso eng
dc.publisher Bentham Science Publ Ltd
dc.relation.ispartof Current Topics In Medicinal Chemistry
dc.rights Acesso restrito
dc.subject adipocyte en
dc.subject ESR1 en
dc.subject ESR2 en
dc.subject glucose uptake en
dc.subject GLUT4 en
dc.subject NF-kappa B en
dc.subject PPT en
dc.subject Slc2a4 en
dc.title Estrogen Receptor 1 Agonist PPT Stimulates Slc2a4 Gene Expression and Improves Insulin-Induced Glucose Uptake in Adipocytes en
dc.type Resenha
dc.contributor.institution Universidade de São Paulo (USP)
dc.contributor.institution Universidade Federal de São Paulo (UNIFESP)
dc.description.affiliation Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, BR-05508900 Sao Paulo, Brazil
dc.description.affiliation Univ Fed Sao Paulo, Dept Pharmacol, Escola Paulista Med, Sect Expt Endocrinol, Sao Paulo, Brazil
dc.description.affiliationUnifesp Univ Fed Sao Paulo, Dept Pharmacol, Escola Paulista Med, Sect Expt Endocrinol, Sao Paulo, Brazil
dc.description.sponsorshipID FAPESP: 2007/50554-1
dc.description.sponsorshipID FAPESP: 2009/02217-1
dc.identifier.doi 10.2174/1568026611212190004
dc.description.source Web of Science
dc.identifier.wos WOS:000313783700004



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