Estradiol stimulates Akt, AMP-activated protein kinase (AMPK) and TBC1D1/4, but not glucose uptake in rat soleus.
Post-menopausal women exhibit decreases in circulating estrogen levels and whole body insulin sensitivity, suggesting that estrogen regulates skeletal muscle glucose disposal. Thus, we assessed whether estrogen stimulates glucose uptake or enhances insulin sensitivity in skeletal muscle. Ex vivo muscle stimulation with 17beta-estradiol (10 nM) resulted in a rapid (10 min) increase in the phosphorylation of Akt, AMP-activated protein kinase (AMPK), and TBC1D1/4, key signaling proteins that regulate glucose uptake in muscle. Treatment with the estrogen receptor antagonist, ICI 182,780, only partly inhibited signaling, suggesting both an estrogen receptor-dependent and independent mechanism of estradiol action. 17beta-Estradiol did not stimulate ex vivo muscle [(3)H]-2-deoxyglucose uptake or enhance insulin-induced glucose uptake, demonstrating discordance between the estradiol-induced stimulation of signaling proteins and muscle glucose uptake. This study is the first to demonstrate that estradiol stimulates Akt, AMPK, and TBC1D1/4 in intact skeletal muscle, but surprisingly, estradiol does not stimulate muscle glucose uptake.
Rogers
Nicole H
NH
Obesity and Metabolism, JM-USDA HNRCA at Tufts University, Boston, MA 02111, USA.
Witczak
Carol A
CA
Hirshman
Michael F
MF
Goodyear
Laurie J
LJ
Greenberg
Andrew S
AS
D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D004958:Estradiol / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D020690:GTPase-Activating Proteins / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D004967:Estrogens; D020690:GTPase-Activating Proteins; D011506:Proteins; C540572:TBC1D1 protein, rat; C533101:TBC1D4 protein, rat; D004958:Estradiol; D051057:Proto-Oncogene Proteins c-akt; D055372:AMP-Activated Protein Kinases; D005947:Glucose