title: Insulin resistance of pregnancy involves estrogen-induced repression of muscle GLUT4.
abstract: Pregnancy is accompanied by hyperestrogenism, however, the role of estrogens in the gestational-induced insulin resistance is unknown. Skeletal muscle plays a fundamental role in this resistance, where GLUT4 regulates glucose uptake. We investigated: (1) effects of oophorectomy and estradiol (E2) on insulin sensitivity and GLUT4 expression. E2 ( approximately 200nM) for 7 days decreased sensitivity, reducing approximately 30% GLUT4 mRNA and protein (P<0.05) and plasma membrane expression in muscle; (2) the expression of ERalpha and ERbeta in L6 myotubes, showing that both coexpress in the same nucleus; (3) effects of E2 on GLUT4 in L6, showing a time- and dose-dependent response. High concentration (100nM) for 6 days reduced approximately 25% GLUT4 mRNA and protein (P<0.05). Concluding, E2 regulates GLUT4 in muscle, and at high concentrations, such as in pregnancy, reduces GLUT4 expression and, in vivo, decreases insulin sensitivity. Thus, hyperestrogenism may be involved in the pregnancy-induced insulin resistance and/or gestational diabetes.
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes, 1524 São Paulo, SP 05508-900, Brazil. Rodrigo.Barros@ki.se
authors.forename: Rodrigo Palazzo De Almeida
authors.initials: RP
authors.lastname: Barros
authors.forename: Andrea
authors.initials: A
authors.lastname: Morani
authors.forename: Anselmo
authors.initials: A
authors.lastname: Moriscot
authors.forename: Ubiratan Fabres
authors.initials: UF
authors.lastname: Machado
mesh_terms: D000818:Animals; D016640:Diabetes, Gestational / Q000378:metabolism* / Q000503:physiopathology; D015536:Down-Regulation; D004958:Estradiol / Q000008:administration & dosage / Q000378:metabolism*; D047628:Estrogen Receptor alpha / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism*; D007279:Injections, Subcutaneous; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D018482:Muscle, Skeletal / Q000378:metabolism*; D032448:Myoblasts, Skeletal / Q000378:metabolism*; D010052:Ovariectomy; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D051275:Glucose Transporter Type 4; D007328:Insulin; D012333:RNA, Messenger; C495694:Slc2a4 protein, rat; D004958:Estradiol; D005947:Glucose