Journal of Obesity & Metabolic Syndrome



J Obes Metab Syndr 2017; 26(1): 78-79

Published online March 30, 2017

Copyright © Korean Society for the Study of Obesity.

17Beta-estradiol Stimulates Glucose Uptake Through Estrogen Receptor and AMP-activated Protein Kinase Activation in C2C12 Myotubes (Korean J Obes 2016;25:190-6)

Ki-Ho Lee1, Kyung-Jin Jo2, Ju-Young Kim3, Haing-Woon Baik1, and Seong-Kyu Lee 1,4,*

1Department of Biochemistry-Molecular Biology, Eulji University School of Medicine, Daejeon, Korea;
2Department of Life Sciences, Pohang University of Science and Technology, Pohang, Korea;
3Imaging Science-based Lung and Bone Diseases Research Center, Wonkwang University, Iksan, Korea;
4Department of Internal Medicine, Eulji University Hospital, Daejeon, Korea

Correspondence to:
Seong-Kyu Lee Department of Biochemistry-Molecular Biology, School of Medicine, Eulji University, 77 Gyeryong-ro 771 beon-gil, Jung-gu, Daejeon 34824, Korea Tel: +82-42-259-1642 Fax +82-42-259-1539 E-mail:

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Long-term 17beta-estradiol treatment protects against obesity, glucose intolerance and insulin resistance in obese and insulin-resistant ovariectomized rodents1-3, and long-term hormone therapy prevents diabetes mellitus due to alterations in body fat distribution and insulin sensitivity, but short-term hormone therapy does not provide complete protection in postmenopausal women.4,5

17beta-estradiol acts predominantly through genomic pathways and regulates the expression of a number of genes by binding to estrogen receptor α and β.6 However, the activation of non-genomic or rapid signaling pathways in response to 17beta-estradiol has attracted increasing attention.7,8 Acute treatment (≤10 minutes) with 17beta-estradiol rapidly increases the phosphorylation of Akt and AMPK, possibly through non-genomic effects, while it does not stimulate glucose uptake or enhance insulin sensitivity in skeletal muscles (rat soleus) ex vivo.9 We investigated whether 24-hour treatment with 17beta-estradiol stimulates glucose uptake and regulates the expression of genes associated with glucose metabolism through the genomic effects of estrogen receptor in C2C12 myotubes. In this study, 24-hour treatment with 17beta-estradiol stimulated glucose uptake, but 30-minute treatment did not. We could not determine the potential mechanisms through which 17beta-estradiol stimulated the expression of genes associated with glucose uptake in C2C12 myotubes, which was a limitation of the study. Further investigation of possible mechanisms will be needed.

As a reader mentioned, mitochondria may be associated with a potential mechanism by which 17beta-estradiol treatment stimulates glucose uptake in C2C12 myotubes, and AMPK stimulates mitochondrial biogenesis by regulating PGC-1α, which in turn promotes transcription of genes in mitochondria and the anti-oxidant defense system.10 We could not investigate these mechanisms. We postulate that 17beta-estradiol regulates the expression of genes associated with glucose metabolism through the genomic effects of estrogen receptor in promoters of genes associated with glucose metabolism.

As a reader suggested, the role of estrogen in mitochondria, which is associated with glucose uptake in skeletal muscle, remains to be investigated, and measurement of the effects of estrogen on fatty acid oxidation in skeletal muscle would also be useful. We agree that these avenues of future research could provide insight into the mechanism of action of 17beta-estradiol in glucose metabolism.

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