Insulin resistance of pregnancy involves estrogen-induced repression of muscle GLUT4

Author(s)

De Almeida Barros, Rodrigo Palazzo ^[1] ; Morani, Andrea ^[2] ; Moriscot, Anselmo ^[3] ; Machado, Ubiratan Fabres ^[4]

Affiliation

^[1] Karolinska Inst. Novum

^[2] Karolinska Inst. Novum

^[3] Univ Sao Paulo. Inst Biomed Sci

^[4] Univ Sao Paulo. Inst Biomed Sci

• Document type: Journal article
• Source: Molecular and Cellular Endocrinology; v. 295, n. 1-2, p. 24-31, NOV 25 2008.
• Web of Science Citations: 41

Abstract

Pregnancy is accompanied by hyperestrogenism, however, the role of estrogens in the gestational-induced insulin resistance is unknown. Skeletal muscle plays a fundamental role in this resistance, where GLUT4 regulates glucose uptake. We investigated: (1) effects of oophorectomy and estradiol (E2) on insulin sensitivity and GLUT4 expression. E2 (similar to 200 nM) for 7 days decreased sensitivity, reducing similar to 30% GLUT4 mRNA and protein (P< 0.05) and plasma membrane expression in muscle; (2) the expression of ER alpha and ER beta in L6 myotubes, showing that both coexpress in the same nucleus; (3) effects of E2 on GLUT4 in L6, showing a time- and dose-dependent response. High concentration (100 nM) for 6 days reduced similar to 25% GLUT4 mRNA and protein (P < 0.05). Concluding, E2 regulates GLUT4 in muscle, and at high concentrations, such as in pregnancy, reduces GLUT4 expression and, in vivo, decreases insulin sensitivity. Thus, hyperestrogenism may be involved in the pregnancy-induced insulin resistance and/or gestational diabetes. (C) 2008 Elsevier Ireland Ltd. All rights reserved. (AU)

• FAPESP's process: 02/07384-4 - Regulation of glucose transporters gene expression in Diabetes Mellitus: Pathophysiological role and potential preventive and therapeutical approaches
• Grantee: Ubiratan Fabres Machado
• Support Opportunities: Research Projects - Thematic Grants