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.

Interaction Between Insulin and Estradiol in Regulation of Cardiac Glucose and Free Fatty Acid Transporters

“…Expectedly, insulin, with or without estradiol, decreased glucose level in all analyzed intervals, while E2 alone showed only nonsignifi cant tendency to decrease glucose level ( • ▶ Table 1 ). Neither insulin nor E2, given separately or simultaneously, altered FFA level within analyzed time interval ( • ▶ Table 1 ) and the absence of eff ect in the present study could be a consequence of short time between treatment and analysis [ 31 ] . Our results concerning timing and extent of insulin eff ect on cardiac membrane GLUT4 ( • ▶ Fig.…”

Effects of obesity and estradiol on Na+/K+-ATPase and their relevance to cardiovascular diseases

“…The activation of Akt in a genderdependent manner may help explain functional benefits for the heart provided by estrogenic stimulation and also differences in CV disease risks between the sexes (Camper-Kirby et al 2001). In the CV system, the activation of estrogen receptor a (ERa) by estradiol has been shown to activate PI3K through the binding of phosphotyrosine-containing proteins such as insulin receptor substrate-1 (IRS1) and IRS2 and the association of p85 with IRS1 in different types of cells (Mauro et al 2001, Isenovic et al 2003, Sudar et al 2008, Koricanac et al 2009). Some authors, including our team, have already described an inducing effect of estradiol on Akt serine (Ser 473 ) phosphorylation, but data concerning threonine (Thr 308 ) are rare (Ren et al 2003, Patten et al 2004, Koricanac et al 2011.…”

A high fat diet induces sex-specific differences in hepatic lipid metabolism and nitrite/nitrate in rats

“…The risk of obesity related metabolic disorders and diabetes is well established in men, but less so for age matched pre-menopausal women [11]. Estradiol has a pivotal role in the protection against IR, since it regulates carbohydrate and lipid metabolism [12,13]. A…”