Participation of ERα and ERβ in glucose homeostasis in skeletal muscle and white adipose tissue

Rodrigo P.A. Barros, Chiara Gabbi, Andrea Morani, Margaret Warner, Jan Åke Gustafsson

Research output: Contribution to journalArticlepeer-review

126 Scopus citations


Glucose uptake and homeostasis are regulated mainly by skeletal muscle (SM), white adipose tissue (WAT), pancreas, and the liver. Participation of estradiol in this regulation is still under intense investigation. We have demonstrated that, in SM of male mice, expression of the insulin-regulated glucose transporter (GLUT)4 is reduced by estrogen receptor (ER)β agonists. In the present study, to investigate the relative contributions of ERα and ERβ in glucose homeostasis, we examined the effects of tamoxifen (Tam) on GLUT4 expression in SM and WAT in wild-type (WT) and ER-/- mice. ERβ-/- mice were characterized by fasting hypoglycemia, increased levels of SM GLUT4, pancreatic islet hypertrophy, and a belated rise in plasma insulin in response to a glucose challenge. ERα-/- mice, on the contrary, were hyperglycemic and glucose intolerant, and expression of SM GLUT4 was markedly lower than in WT mice. Tam had no effect on glucose tolerance or insulin sensitivity in WT mice. In ERα-/- mice, Tam increased GLUT4 and improved insulin sensitivity. i.e., it behaved as an ERβ antagonist in SM but had no effect on WAT. In ERβ-/- mice, Tam did not affect GLUT4 in SM but acted as an ERα antagonist in WAT, decreasing GLUT4. Thus, in the interplay between ERα and ERβ, ERβ-mediated repression of GLUT4 predominates in SM but ERα-mediated induction of GLUT4 predominates in WAT. This tissue-specific difference in dominance of one ER over the other is reflected in the ratio of the expression of the two receptors. ERα predominates in WAT and ERβ in SM.

Original languageEnglish (US)
Pages (from-to)E124-E133
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Issue number1
StatePublished - Jul 2009


  • Estrogen receptor-α
  • Estrogen receptor-β
  • Glucose transporter 4
  • Tamoxifen

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Endocrinology, Diabetes and Metabolism
  • Medicine(all)


Dive into the research topics of 'Participation of ERα and ERβ in glucose homeostasis in skeletal muscle and white adipose tissue'. Together they form a unique fingerprint.

Cite this