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

Autor: Meister J; Molecular Signaling Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 20892, USA. meister.jaro@gmail.com., Bone DBJ; Molecular Signaling Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 20892, USA., Knudsen JR; Departments of Nutrition, Exercise and Sports, University of Copenhagen, København, Denmark., Barella LF; Molecular Signaling Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 20892, USA., Velenosi TJ; Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada., Akhmedov D; Departments of Integrative Biology and Pharmacology, Houston Medical School, Houston, TX, 77030, USA., Lee RJ; Molecular Signaling Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 20892, USA., Cohen AH; Molecular Signaling Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 20892, USA., Gavrilova O; Mouse Metabolism Core, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 20892, USA., Cui Y; Molecular Signaling Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 20892, USA., Karsenty G; Departments of Genetics and Development, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA., Chen M; Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 20892, USA., Weinstein LS; Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 20892, USA., Kleinert M; Departments of Nutrition, Exercise and Sports, University of Copenhagen, København, Denmark.; Muscle Physiology and Metabolism Group, German Institute of Human Nutrition, Potsdam-Rehbrücke, Nuthetal, Germany., Berdeaux R; Departments of Integrative Biology and Pharmacology, Houston Medical School, Houston, TX, 77030, USA., Jensen TE; Departments of Nutrition, Exercise and Sports, University of Copenhagen, København, Denmark., Richter EA; Departments of Nutrition, Exercise and Sports, University of Copenhagen, København, Denmark., Wess J; Molecular Signaling Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 20892, USA. jurgenw@niddk.nih.gov.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2022 Jan 10; Vol. 13 (1), pp. 22. Date of Electronic Publication: 2022 Jan 10.
DOI: 10.1038/s41467-021-27540-w
Abstrakt: 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 β 2 -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 β 2 -adrenergic receptors and the stimulatory G protein, G s . Unbiased transcriptomic and metabolomic analyses showed that chronic β 2 -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 β 2 -adrenergic receptor-dependent signaling pathways may prove beneficial as antidiabetic drugs.
(© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)
Databáze: MEDLINE
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