Korean J Obes.  2016 Dec;25(4):190-196. 10.7570/kjo.2016.25.4.190.

17Beta-estradiol Stimulates Glucose Uptake Through Estrogen Receptor and AMP-activated Protein Kinase Activation in C2C12 Myotubes

• Lee KH
• Jo KJ
• Kim JY
• Baik HW
• Lee SK

• KMID: 2368798
• DOI: http://doi.org/10.7570/kjo.2016.25.4.190

Abstract

BACKGROUND
Previous studies have shown that 17beta-estradiol activates AMP-activated protein kinase (AMPK) in rodent muscle and C2C12 myotubes and that acute 17beta-estradiol treatment rapidly increases AMPK phosphorylation possibly through non-genomic effects but does not stimulate glucose uptake. Here, we investigated whether 24-hour 17beta-estradiol treatment stimulated glucose uptake and regulated the expression of genes associated with glucose and energy metabolism through the genomic effects of estrogen receptor (ER) in C2C12 myotubes.
METHODS
C2C12 myotubes were treated with 17beta-estradiol for 24 hours, and activation of AMPK, uptake of glucose, and expression of genes encoding peroxisome proliferator-activated receptor γ coactivator 1α, carnitine palmitoyltransferase 1β, uncoupling protein 2, and glucose transporter 4 were examined. Furthermore, we investigated whether AMPK inhibitor (compound C) or estrogen receptor antagonist (ICI182.780) treatment reversed 17beta-estradiol-induced changes.
RESULTS
We found that 24-hour treatment of C2C12 myotubes with 17beta-estradiol stimulated AMPK activation and glucose uptake and regulated the expression of genes associated with glucose and energy metabolism. Treatment of C2C12 myotubes with the estrogen receptor antagonist (ICI182.780) reversed 17beta-estradiol-induced AMPK activation, glucose uptake, and changes in the expression of target genes. Furthermore, treatment with the AMPK inhibitor (compound C) reversed 17beta-estradiol-induced glucose uptake and changes in the expression of target genes.
CONCLUSION
Our results suggest that 17beta-estradiol stimulates AMPK activation and glucose uptake and regulates the expression of genes associated with glucose and energy metabolism in C2C12 myotubes through the genomic effects of ER.

Keyword

17Beta-estradiol; Estrogen receptor; AMP-activated protein kinase; Glucose uptake

MeSH Terms

AMP-Activated Protein Kinases*
Carnitine O-Palmitoyltransferase
Energy Metabolism
Estrogens*
Glucose Transport Proteins, Facilitative
Glucose*
Muscle Fibers, Skeletal*
Peroxisomes
Phosphorylation
Rodentia
AMP-Activated Protein Kinases
Carnitine O-Palmitoyltransferase
Estrogens
Glucose
Glucose Transport Proteins, Facilitative