title: Effects of estradiol and genistein on the insulin signaling pathway in the cerebral cortex of aged female rats.
abstract: Menopause leads to a decrease in estrogen production that increases central insulin resistance, contributing to the development of neurodegenerative diseases. We have evaluated the influence of aging and estradiol or genistein treatments on some key stages of the insulin signaling pathway in the cerebral cortex. Young and aged female Wistar rats were ovariectomized and treated acutely with 17β-estradiol (1.4μg/kg body weight), two doses of genistein (10 or 40mg/kg body weight), or vehicle. The cortical expression of several key insulin signaling pathway components was analyzed by western blotting. Our results showed an age-related deterioration in the interactions between the regulatory subunit of phosphatidylinositol 3-kinase (p85α) and the activated form of insulin receptor substrate 1 (p-IRS1tyr612), as well as between p85α and the 46kDa isoform of the estrogen receptor α (ERα46). Moreover, aging also decreased the translocation of glucose transporter-4 (GLUT4) to the plasma membrane. 17β-Estradiol but not genistein reduced the negative impact of aging on central insulin sensitivity by favoring this GLUT4 translocation, and therefore could be neuroprotective against the associated neurodegenerative diseases. However, protein kinase B (Akt) activation by genistein suggests that other possible mechanisms are involved in the neuroprotective effects of this phytoestrogen during the aging process.
authors.affiliation: Department of Functional Biology, Physiology Area, University of Oviedo, Av. Julián Clavería, No. 6, 33006 Oviedo, Spain. Electronic address: moransuarezjavier@gmail.com.
authors.forename: Javier
authors.initials: J
authors.lastname: Morán
authors.affiliation: Department of Functional Biology, Physiology Area, University of Oviedo, Av. Julián Clavería, No. 6, 33006 Oviedo, Spain. Electronic address: garridocuestapablo@gmail.com.
authors.forename: Pablo
authors.initials: P
authors.lastname: Garrido
authors.affiliation: Department of Functional Biology, Physiology Area, University of Oviedo, Av. Julián Clavería, No. 6, 33006 Oviedo, Spain. Electronic address: estefaniacabello84@hotmail.com.
authors.forename: Estefanía
authors.initials: E
authors.lastname: Cabello
authors.affiliation: Department of Functional Biology, Physiology Area, University of Oviedo, Av. Julián Clavería, No. 6, 33006 Oviedo, Spain. Electronic address: alonsoana@uniovi.es.
authors.forename: Ana
authors.initials: A
authors.lastname: Alonso
authors.affiliation: Department of Functional Biology, Physiology Area, University of Oviedo, Av. Julián Clavería, No. 6, 33006 Oviedo, Spain. Electronic address: tinog@uniovi.es.
authors.forename: Celestino
authors.initials: C
authors.lastname: González
mesh_terms: D000367:Age Factors; D000375:Aging; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D058543:Class Ia Phosphatidylinositol 3-Kinase / Q000378:metabolism; D004789:Enzyme Activation; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000819:agonists / Q000378:metabolism; D005260:Female; D019833:Genistein / Q000494:pharmacology*; D051275:Glucose Transporter Type 4 / Q000187:drug effects / Q000378:metabolism; D020249:Hormone Replacement Therapy; D007328:Insulin / Q000378:metabolism*; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D010052:Ovariectomy; D010766:Phosphorylation; D048789:Phytoestrogens / Q000494:pharmacology*; D021381:Protein Transport; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D047628:Estrogen Receptor alpha; D051275:Glucose Transporter Type 4; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D048789:Phytoestrogens; C495694:Slc2a4 protein, rat; D004958:Estradiol; D019833:Genistein; D058543:Class Ia Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt
keywords: 17β-Estradiol; Cerebral cortex; Female aging; Genistein; Insulin signaling pathway; Rat