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

Marta Garcia-Arevalo, Estela Lorza-Gil, Nayara Leite, Sergio Brunetto, Antonio Carlos Boschero, Everardo Magalhaes Carneiro

Abstract


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 ? 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 µg/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?, which interacts directly with phosphatidylinositol 3-kinase (PI3K), increasing the phosphorylation of AKT and consequently, glucose uptake in muscle.




J Endocrinol Metab. 2019;9(5):133-146
doi: https://doi.org/10.14740/jem612


Keywords


Insulin sensitivity; Estradiol; Estrogen receptor alpha; Low protein diet; Malnourishment

Full Text: HTML PDF Suppl1 Suppl2 Suppl3 Suppl4 Suppl5 Suppl6 Video 1 Video 2
 

Browse  Journals  

     

Journal of clinical Medicine Research

Journal of Endocrinology and Metabolism

Journal of Clinical Gynecology and Obstetrics

World Journal of Oncology

Gastroenterology Research

Journal of Hematology

Journal of Medical Cases

Journal of Current Surgery

Clinical Infection and Immunity

Cardiology Research

World Journal of Nephrology and Urology

Cellular and Molecular Medicine Research

Journal of Neurology Research

International Journal of Clinical Pediatrics

 

 

 

 

 

Journal of Endocrinology and Metabolism, bimonthly, ISSN 1923-2861 (print), 1923-287X (online), published by Elmer Press Inc.        
The content of this site is intended for health care professionals.
This is an open-access journal distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License, which permits unrestricted
non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Creative Commons Attribution license (Attribution-NonCommercial 4.0 International CC-BY-NC 4.0)


This journal follows the International Committee of Medical Journal Editors (ICMJE) recommendations for manuscripts submitted to biomedical journals,
the Committee on Publication Ethics (COPE) guidelines, and the Principles of Transparency and Best Practice in Scholarly Publishing.

website: www.jofem.org   editorial contact: editor@jofem.org
Address: 9225 Leslie Street, Suite 201, Richmond Hill, Ontario, L4B 3H6, Canada

© Elmer Press Inc. All Rights Reserved.