Chronic 17β-estradiol treatment improves skeletal muscle insulin signaling pathway components in insulin resistance associated with aging

Abstract

Insulin resistance is a common feature of aging in both humans and rats. In the case of females, it seems to be related to loss of gonadal function, due mainly due to a decrease in plasma estrogen levels. Several causes have been postulated for this insulin resistance, among them changes in several steps of the insulin pathway. In view of these findings, the purpose of the present study was to examine the role of chronic 17β-estradiol treatment on insulin sensitivity during the aging process, and its effects on levels of the insulin-sensitive glucose transporter Glut4 (both total and plasma membrane localized), the interaction between p85α subunit of PI3-k and IRS-1, Tyr-and Ser-612 phosphorylation of IRS-1 levels, and Ser-473 phosphorylation of Akt. The present findings indicate that 17β-estradiol treatment is able to minimize the deleterious effect of aging on insulin sensitivity, at least at the level of plasma membrane localized Glut4. Nevertheless further research is needed to determine this conclusively.

GPER1 is regulated by insulin in cancer cells and cancer-associated fibroblasts

“…Results from previous studies have indicated that estrogens increase insulin sensitivity and stimulate glucose uptake upon acute and chronic exposure to these steroids in target tissues as well as in ESR1-positive breast cancer cells (Alonso et al 2006, Moreno et al 2010, Garrido et al 2013. On the basis of these findings and considering that GPER1 has been shown to be involved in insulinregulated metabolic functions in both mice and humans (Mårtensson et al 2009, Kumar et al 2011, Sharma & Prossnitz 2013, we have also ascertained that GPER1 mediates the glucose uptake induced by estrogens in CAFs and SKUT-1 cells.…”

Aging and substitutive hormonal therapy influence in regional and subcellular distribution of ERα in female rat brain

“…Plasma 17β-estradiol values obtained during the study were previously published in recent papers of our group (Moreno et al 2010;Pérez et al 2011). The plasma level of 17β-estradiol was significantly higher in groups E and C than in group O at all time points.…”

Glucosamine-induced insulin resistance in ovariectomized rats is relevant to decreasing the expression of glucose transport protein subtype 4 in the skeletal muscle and in increasing the size of pancreatic islets

“…Our result is compatible with the previous study using Sprague-Dawley rats that demonstrated that the absence of ovarian hormone, particularly estrogen, had no influence on GLUT-4 protein 63 ; even though the other study using Wistar rats indicated a different result on the effect of ovariectomy on GLUT-4 expression. 64 Perhaps different animal models lead to different results. The relationship between GlcN and GLUT-4 was rarely discussed.…”