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- Title
Clenbuterol exerts antidiabetic activity through metabolic reprogramming of skeletal muscle cells.
- Authors
Meister, Jaroslawna; Bone, Derek B. J.; Knudsen, Jonas R.; 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 E.; Richter, Erik A.; Wess, Jürgen
- Abstract
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. In this study, the authors demonstrated that agents targeting skeletal muscle metabolism by modulating β2-adrenergic receptor-dependent signaling may prove beneficial as novel antidiabetic drugs.
- Subjects
ADRENERGIC receptors; SKELETAL muscle; G protein coupled receptors; MUSCLE cells; CLENBUTEROL; SYMPATHETIC nervous system; HYPOGLYCEMIC agents
- Publication
Nature Communications, 2022, Vol 13, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-021-27540-w