Clenbuterol exerts antidiabetic activity through metabolic reprogramming of skeletal muscle cells
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Clenbuterol exerts antidiabetic activity through metabolic reprogramming of skeletal muscle cells. / Meister, Jaroslawna; Bone, Derek B J; Knudsen, Jonas Roland; Barella, Luiz F; Velenosi, Thomas J; Akhmedov, Dmitry; Lee, Regina J; Cohen, Amanda H; Gavrilova, Oksana; Cui, Yinghong; Karsenty, Gerard; Chen, Min; Weinstein, Lee S; Kleinert, Maximilian; Berdeaux, Rebecca; Jensen, Thomas Elbenhardt; Richter, Erik A.; Wess, Jürgen.
In: Nature Communications, Vol. 13, 22, 2022.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Clenbuterol exerts antidiabetic activity through metabolic reprogramming of skeletal muscle cells
AU - Meister, Jaroslawna
AU - Bone, Derek B J
AU - Knudsen, Jonas Roland
AU - Barella, Luiz F
AU - Velenosi, Thomas J
AU - Akhmedov, Dmitry
AU - Lee, Regina J
AU - Cohen, Amanda H
AU - Gavrilova, Oksana
AU - Cui, Yinghong
AU - Karsenty, Gerard
AU - Chen, Min
AU - Weinstein, Lee S
AU - Kleinert, Maximilian
AU - Berdeaux, Rebecca
AU - Jensen, Thomas Elbenhardt
AU - Richter, Erik A.
AU - Wess, Jürgen
N1 - © 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.
PY - 2022
Y1 - 2022
N2 - Activation of the sympathetic nervous system causes pronounced metabolic changes that are mediated by multiple adrenergic receptor subtypes. Systemic treatment with β2-adrenergic receptor agonists results in multiple beneficial metabolic effects, including improved glucose homeostasis. To elucidate the underlying cellular and molecular mechanisms, we chronically treated wild-type mice and several newly developed mutant mouse strains with clenbuterol, a selective β2-adrenergic receptor agonist. Clenbuterol administration caused pronounced improvements in glucose homeostasis and prevented the metabolic deficits in mouse models of β-cell dysfunction and insulin resistance. Studies with skeletal muscle-specific mutant mice demonstrated that these metabolic improvements required activation of skeletal muscle β2-adrenergic receptors and the stimulatory G protein, Gs. Unbiased transcriptomic and metabolomic analyses showed that chronic β2-adrenergic receptor stimulation caused metabolic reprogramming of skeletal muscle characterized by enhanced glucose utilization. These findings strongly suggest that agents targeting skeletal muscle metabolism by modulating β2-adrenergic receptor-dependent signaling pathways may prove beneficial as antidiabetic drugs.
AB - Activation of the sympathetic nervous system causes pronounced metabolic changes that are mediated by multiple adrenergic receptor subtypes. Systemic treatment with β2-adrenergic receptor agonists results in multiple beneficial metabolic effects, including improved glucose homeostasis. To elucidate the underlying cellular and molecular mechanisms, we chronically treated wild-type mice and several newly developed mutant mouse strains with clenbuterol, a selective β2-adrenergic receptor agonist. Clenbuterol administration caused pronounced improvements in glucose homeostasis and prevented the metabolic deficits in mouse models of β-cell dysfunction and insulin resistance. Studies with skeletal muscle-specific mutant mice demonstrated that these metabolic improvements required activation of skeletal muscle β2-adrenergic receptors and the stimulatory G protein, Gs. Unbiased transcriptomic and metabolomic analyses showed that chronic β2-adrenergic receptor stimulation caused metabolic reprogramming of skeletal muscle characterized by enhanced glucose utilization. These findings strongly suggest that agents targeting skeletal muscle metabolism by modulating β2-adrenergic receptor-dependent signaling pathways may prove beneficial as antidiabetic drugs.
U2 - 10.1038/s41467-021-27540-w
DO - 10.1038/s41467-021-27540-w
M3 - Journal article
C2 - 35013148
VL - 13
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 22
ER -
ID: 289308321