| First Author | Meister J | Year | 2022 |
| Journal | Nat Commun | Volume | 13 |
| Issue | 1 | Pages | 22 |
| PubMed ID | 35013148 | Mgi Jnum | J:369716 |
| Mgi Id | MGI:6857206 | Doi | 10.1038/s41467-021-27540-w |
| Citation | Meister J, et al. (2022) Clenbuterol exerts antidiabetic activity through metabolic reprogramming of skeletal muscle cells. Nat Commun 13(1):22 |
| abstractText | Activation of the sympathetic nervous system causes pronounced metabolic changes that are mediated by multiple adrenergic receptor subtypes. Systemic treatment with beta2-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 beta2-adrenergic receptor agonist. Clenbuterol administration caused pronounced improvements in glucose homeostasis and prevented the metabolic deficits in mouse models of beta-cell dysfunction and insulin resistance. Studies with skeletal muscle-specific mutant mice demonstrated that these metabolic improvements required activation of skeletal muscle beta2-adrenergic receptors and the stimulatory G protein, Gs. Unbiased transcriptomic and metabolomic analyses showed that chronic beta2-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 beta2-adrenergic receptor-dependent signaling pathways may prove beneficial as antidiabetic drugs. |
