Fig. 4: ERα increases IRS1 protein stability and promotes hepatic insulin sensitivity.
From: An estrogen receptor α-derived peptide improves glucose homeostasis during obesity
a Insulin signaling activity in primary hepatocytes from ERαF/F and ERαLivKO male mice, n = 3 independent cells; for IRS1, ERαF/F-Vehicle versus ERαLivKO-Vehicle, P < 0.0001, ERαF/F-Insulin versus ERαLivKO-Insulin, P < 0.0001; for pAKT-S473, ERαF/F-Vehicle versus ERαF/F-Insulin, P < 0.0001, ERαLivKO-Vehicle versus ERαLivKO-Insulin, P = 0.0186, ERαF/F-Insulin versus ERαLivKO-Insulin, P < 0.0001; for ERα, ERαF/F-Vehicle versus ERαLivKO-Vehicle, P = 0.0002, ERαF/F-Insulin versus ERαLivKO-Insulin, P = 0.0001. b Effect of ERα gain-of-function on hepatic insulin sensitivity. The experiments were repeated independently twice. Representative blots were shown. c Effect of ERα deletion on insulin-induced IRS1 and p85 interaction. The experiments were repeated independently twice. Representative blots were shown. d Effect of ERα gain-of-function on insulin-induced IRS1 and p85 interaction. The experiments were repeated independently twice. Representative blots were shown. e Effect of ERα deletion on mRNA expression of Irs1 and Irs2 in primary mouse hepatocytes, n = 4 (ERαF/F) and 5 (ERαLivKO); for ERα, P = 0.0001. f Interaction between ERα and IRS1 or IRS2 in HEK293T cells. The experiments were repeated independently three times. Representative blots were shown. g Effect of ERα on IRS1 ubiquitination in HEK293T cells. The experiments were repeated independently twice. Representative blots were shown. h Effect of ERα on IRS2 ubiquitination in HEK293T cells. The experiments were repeated independently twice. Representative blots were shown. i Effect of ERα deletion on IRS1 ubiquitination in primary mouse hepatocytes. The experiments were repeated independently twice. Representative blots were shown. j Diagram of IRS1 and its truncated domains. k Interaction between ERα and IRS1 domains in HEK293T cells. The experiments were repeated independently three times. Representative blots were shown. l Effect of ERα deletion on IRS1 phosphorylation in primary mouse hepatocytes, n = 3 independent cells; for IRS1, P = 0.0102; for pIRS1-S302, P = 0.0236. m Effect of ERα gain-of-function on palmitate-induced insulin resistance in primary mouse hepatocytes. The experiments were repeated independently twice. Representative blots were shown. Data are presented as mean ± SEM. *P < 0.05, ***P < 0.001, ****P < 0.0001, unpaired Two-tailed Student’s t test (e and l), Two-way ANOVA with Tukey’s multiple comparisons test (a). Source data are provided as a Source Data file.
