Participation of ERα and ERβ in glucose homeostasis in skeletal muscle and white adipose tissue
Autor: | Margaret Warner, Andrea Morani, Chiara Gabbi, Rodrigo P.A. Barros, Jan-Ake Gustafsson |
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Rok vydání: | 2009 |
Předmět: |
Blood Glucose
Male medicine.medical_specialty Physiology Adipose Tissue White Endocrinology Diabetes and Metabolism Glucose uptake Adipose tissue White adipose tissue Biology Carbohydrate metabolism Mice Physiology (medical) Internal medicine medicine Animals Estrogen Receptor beta Homeostasis Insulin Glucose homeostasis Muscle Skeletal Mice Knockout Glucose tolerance test Glucose Transporter Type 4 medicine.diagnostic_test Estrogen Receptor alpha nutritional and metabolic diseases Skeletal muscle Glucose Tolerance Test Glucose medicine.anatomical_structure Endocrinology Area Under Curve hormones hormone substitutes and hormone antagonists |
Zdroj: | American Journal of Physiology-Endocrinology and Metabolism. 297:E124-E133 |
ISSN: | 1522-1555 0193-1849 |
Popis: | 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)beta agonists. In the present study, to investigate the relative contributions of ERalpha and ERbeta in glucose homeostasis, we examined the effects of tamoxifen (Tam) on GLUT4 expression in SM and WAT in wild-type (WT) and ER-/- mice. ERbeta-/- 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. ERalpha-/- 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 ERalpha-/- mice, Tam increased GLUT4 and improved insulin sensitivity. i.e., it behaved as an ERbeta antagonist in SM but had no effect on WAT. In ERbeta-/- mice, Tam did not affect GLUT4 in SM but acted as an ERalpha antagonist in WAT, decreasing GLUT4. Thus, in the interplay between ERalpha and ERbeta, ERbeta-mediated repression of GLUT4 predominates in SM but ERalpha-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. ERalpha predominates in WAT and ERbeta in SM. |
Databáze: | OpenAIRE |
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