title: Impact of estradiol on insulin signaling in the rat heart.
abstract: It is well known that variation in the concentration of estrogens affects insulin action. In this study we examine the impact of estradiol (E2) on insulin signaling in the rat heart. Ovariectomized female rats were treated with E2 6 h prior to analysis of basal protein and mRNA content of insulin signaling molecules, and additionally with insulin 30 min before the experiment to delineate E2 effects on phosphorylations and molecular associations relevant for insulin signaling. The results show that E2 decreased insulin receptor (IR) tyrosine phosphorylation, while it did not alter IR protein and mRNA content. E2 administration did not change IR substrate 1 (IRS-1) protein content and tyrosine phosphorylation, while decreased mRNA content and increased its association with the p85 subunit of phosphatidylinositol 3-kinase (PI3K). E2 decreased protein and mRNA content of IR substrate 2 (IRS-2), while did not change IRS-2 tyrosine phosphorylation and IRS-2 association with p85. The increase of IRS-1/p85 is accompanied by increase of p85 protein and mRNA levels, and by stimulation of protein kinase B (Akt) Ser(473) phosphorylation. In contrast, Akt protein and mRNA content were not changed. In summary, although in some aspects cardiac insulin signaling is obviously improved by E2 treatment (increase of p85 mRNA and protein levels, enhancement of IRS-1/p85 association and Ser(473)Akt phosphorylation), the observed decrease of IR tyrosine phosphorylation, IRS-2 protein content, and IRSs mRNA contents, suggest very complex interplay of beneficial and suppressive effects of E2, both genomic and non-genomic, in regulation of heart insulin signaling.
authors.affiliation: Laboratory for Molecular Biology and Endocrinology, Vinca Institute of Nuclear Sciences, Belgrade, Serbia. gogi@vinca.rs
authors.forename: Goran
authors.initials: G
authors.lastname: Koricanac
authors.forename: Tijana
authors.initials: T
authors.lastname: Milosavljevic
authors.forename: Mojca
authors.initials: M
authors.lastname: Stojiljkovic
authors.forename: Zorica
authors.initials: Z
authors.lastname: Zakula
authors.forename: Snezana
authors.initials: S
authors.lastname: Tepavcevic
authors.forename: Nevena
authors.initials: N
authors.lastname: Ribarac-Stepic
authors.forename: Esma R
authors.initials: ER
authors.lastname: Isenovic
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D006321:Heart / Q000187:drug effects*; D007328:Insulin / Q000378:metabolism*; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D010052:Ovariectomy; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D013552:Swine
chemical_list: D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; C526299:Irs2 protein, rat; D004958:Estradiol; D019869:Phosphatidylinositol 3-Kinases; D011972:Receptor, Insulin; D051057:Proto-Oncogene Proteins c-akt