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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

The 17-Beta-Estradiol Improves Insulin Sensitivity in a Rapid Estrogen Receptor Alpha-Dependent Manner in an Animal Model of Malnourishment

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Garcia-Arevalo, Marta [1, 2] ; Lorza-Gil, Estela [1] ; Leite, Nayara [1] ; Brunetto, Sergio [3, 4] ; Boschero, Antonio Carlos [1] ; Carneiro, Everardo Magalhaes [1]
Total Authors: 6
[1] Univ Estadual Campinas, UNICAMP, Inst Biol, Dept Struct & Funct Biol, OCRC, Campinas, SP - Brazil
[2] Univ Estadual Campinas, UNICAMP, Inst Biol, OCRC, BR-13083970 Campinas, SP - Brazil
[3] Univ Estadual Campinas, UNICAMP, Med Phys Div, Biomed Engn Ctr, Campinas, SP - Brazil
[4] Univ Estadual Campinas, UNICAMP, Nucl Med Div, Clin Hosp, Campinas, SP - Brazil
Total Affiliations: 4
Document type: Journal article
Source: JOURNAL OF ENDOCRINOLOGY AND METABOLISM; v. 9, n. 5, p. 133-146, OCT 2019.
Web of Science Citations: 0

Background: Protein restriction causes metabolic programming to maintain glucose homeostasis in rodents. They develop increased insulin sensitivity in peripheral tissues and reduced insulin secretion by pancreatic beta cells. Estradiol (E2) is a steroid hormone involved in the control of energy balance and glucose homeostasis. Here, we assessed the role of estrogen receptors (ERs) on glucose homeostasis in malnourished mice and the effect of E2 on insulin signaling. Methods: Post-weaned Swiss male mice were fed a low-protein (LP, 6%) or chow diet (control, 14%) for 8 weeks. The malnourished phenotype in LP mice was confirmed by different physiological parameters. Hypersensitivity to insulin was demonstrated by a higher glucose infusion in the LP group compared with the control by euglycemic-hyperinsulinemic clamp. Results: The administration of 10 mu g/kg E2 during the clamp induced a significant increase in the glucose infusion rate in the LP group compared with the control, indicating enhanced insulin sensitivity in LP mice. In addition, E2 administration increased glucose uptake by peripheral tissues. These effects were blunted in mice treated with general ER antagonists (ICI 182,780 and MPP). However, PHTTP failed to interfere with the E2 effect on insulin sensitivity. In the estradiol LP-treated mice, the activity of the insulin pathway was augmented, as demonstrated by higher AKT phosphorylation and glucose uptake by the skeletal muscle. Conclusion: Thus, we show an acute effect of E2 on insulin signaling in the skeletal muscle of protein-restricted mice. It is mediated by ER alpha, which interacts directly with phosphatidylinositol 3-kinase (PI3K), increasing the phosphorylation of AKT and consequently, glucose uptake in muscle. (AU)

FAPESP's process: 14/09532-8 - Functional and molecular analysis of estrogen receptors in the islets of Langerhans and peripheral tissues of malnourished mice and their involvement in glycemic control
Grantee:Marta García-Arévalo Provencio
Support type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 15/12611-0 - Molecular mechanisms involved in pancreatic beta cell disfunction and dead in diabetes mellitus: strategies for the inhibition of these processes and restoration of the insular mass
Grantee:Antonio Carlos Boschiero
Support type: Research Projects - Thematic Grants
FAPESP's process: 14/01717-9 - Investigation of the insulinotropic, insulinomimetic and endothelial actions of taurine in cells/tissues submitted to an in vitro amino acid restriction: an integrated and multifocal approach
Grantee:Everardo Magalhães Carneiro
Support type: Research Projects - Thematic Grants