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Clenbuterol exerts antidiabetic activity through metabolic reprogramming of skeletal muscle cells

ABSTRACT: Activation of the sympathetic nervous system causes pronounced metabolic changes that are mediated by multiple adrenergic receptor subtypes. Systemic treatment with β_2-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, G_s. 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.

INSTRUMENT(S): Q Exactive

PROVIDER: MTBLS467 | MetaboLights | 2022-08-26

REPOSITORIES: MetaboLights

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			Action	DRS
	QXA10POSEAR20191022_NIDD0119VW_MOUSE_MUSCLE1_03.mzML	Mzml
	QXA10POSEAR20191022_NIDD0119VW_MOUSE_MUSCLE1_04.mzML	Mzml
	QXA10POSEAR20191022_NIDD0119VW_MOUSE_MUSCLE1_05.mzML	Mzml
	QXA10POSEAR20191022_NIDD0119VW_MOUSE_MUSCLE1_06.mzML	Mzml
	QXA10POSEAR20191022_NIDD0119VW_MOUSE_MUSCLE1_08.mzML	Mzml

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Clenbuterol exerts antidiabetic activity through metabolic reprogramming of skeletal muscle cells.

Meister Jaroslawna J Bone Derek B J DBJ Knudsen Jonas R JR Barella Luiz F LF Velenosi Thomas J TJ Akhmedov Dmitry D Lee Regina J RJ Cohen Amanda H AH Gavrilova Oksana O Cui Yinghong Y Karsenty Gerard G Chen Min M Weinstein Lee S LS Kleinert Maximilian M Berdeaux Rebecca R Jensen Thomas E TE Richter Erik A EA Wess Jürgen J

Nature communications 20220110 1

Activation of the sympathetic nervous system causes pronounced metabolic changes that are mediated by multiple adrenergic receptor subtypes. Systemic treatment with β<sub>2-</sub>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 β<sub>2</sub>-adrenerg ...[more]

PMID: 35013148

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