Effect of β2-agonist treatment on insulin-stimulated peripheral glucose disposal in healthy men in a randomised placebo-controlled trial

Sten M. M. Beek, Yvonne M. H. Bruls, Froukje Vanweert, Ciarán E. Fealy, Niels J. Connell, Gert Schaart, Esther Moonen-Kornips, Johanna A. Jörgensen, Frédéric M. Vaz, Ellen T. H. C. Smeets, Peter J. Joris, Anne Gemmink, Riekelt H. Houtkooper, Matthijs K. C. Hesselink, Tore Bengtsson, Bas Havekes, Patrick Schrauwen and Joris Hoeks ()
Additional contact information
Sten M. M. Beek: Maastricht University
Yvonne M. H. Bruls: Maastricht University Medical Center+
Froukje Vanweert: Maastricht University
Ciarán E. Fealy: Maastricht University
Niels J. Connell: Maastricht University
Gert Schaart: Maastricht University
Esther Moonen-Kornips: Maastricht University
Johanna A. Jörgensen: Maastricht University
Frédéric M. Vaz: Amsterdam UMC location University of Amsterdam
Ellen T. H. C. Smeets: Maastricht University
Peter J. Joris: Maastricht University
Anne Gemmink: Maastricht University
Riekelt H. Houtkooper: Amsterdam UMC location University of Amsterdam
Matthijs K. C. Hesselink: Maastricht University
Tore Bengtsson: Stockholm University
Bas Havekes: Maastricht University
Patrick Schrauwen: Maastricht University
Joris Hoeks: Maastricht University

Nature Communications, 2023, vol. 14, issue 1, 1-15

Abstract: Abstract β2-agonist treatment improves skeletal muscle glucose uptake and whole-body glucose homeostasis in rodents, likely via mTORC2-mediated signalling. However, human data on this topic is virtually absent. We here investigate the effects of two-weeks treatment with the β2-agonist clenbuterol (40 µg/day) on glucose control as well as energy- and substrate metabolism in healthy young men (age: 18-30 years, BMI: 20-25 kg/m2) in a randomised, placebo-controlled, double-blinded, cross-over study (ClinicalTrials.gov-identifier: NCT03800290). Randomisation occurred by controlled randomisation and the final allocation sequence was seven (period 1: clenbuterol, period 2: placebo) to four (period 1: placebo, period 2: clenbuterol). The primary and secondary outcome were peripheral insulin-stimulated glucose disposal and skeletal muscle GLUT4 translocation, respectively. Primary analyses were performed on eleven participants. No serious adverse events were reported. The study was performed at Maastricht University, Maastricht, The Netherlands, between August 2019 and April 2021. Clenbuterol treatment improved peripheral insulin-stimulated glucose disposal by 13% (46.6 ± 3.5 versus 41.2 ± 2.7 µmol/kg/min, p = 0.032), whereas skeletal muscle GLUT4 translocation assessed in overnight fasted muscle biopsies remained unaffected. These results highlight the potential of β2-agonist treatment in improving skeletal muscle glucose uptake and underscore the therapeutic value of this pathway for the treatment of type 2 diabetes. However, given the well-known (cardiovascular) side-effects of systemic β2-agonist treatment, further exploration on the underlying mechanisms is needed to identify viable therapeutic targets.

Date: 2023
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DOI: 10.1038/s41467-023-35798-5

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