TY - JOUR
T1 - Effect of β2-agonist treatment on insulin-stimulated peripheral glucose disposal in healthy men in a randomised placebo-controlled trial
AU - van Beek, Sten M. M.
AU - Bruls, Yvonne M. H.
AU - Vanweert, Froukje
AU - Fealy, Ciarán E.
AU - Connell, Niels J.
AU - Schaart, Gert
AU - Moonen-Kornips, Esther
AU - Jörgensen, Johanna A.
AU - Vaz, Frédéric M.
AU - Smeets, Ellen T. H. C.
AU - Joris, Peter J.
AU - Gemmink, Anne
AU - Houtkooper, Riekelt H.
AU - Hesselink, Matthijs K. C.
AU - Bengtsson, Tore
AU - Havekes, Bas
AU - Schrauwen, Patrick
AU - Hoeks, Joris
N1 - Funding Information: This study was supported by a grant from ZonMW and the Dutch Diabetes Research Foundation (J.H.) and the Nutrim NWO graduate program (S.v.B.). Funding agencies had no influence on the study design, data collection and analysis, and manuscript writing. The authors would like to thank Jorg Sander and Martin Vervaart for their assistance during this study. Publisher Copyright: © 2023, The Author(s).
PY - 2023/12/1
Y1 - 2023/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85146194871&partnerID=8YFLogxK
U2 - https://doi.org/10.1038/s41467-023-35798-5
DO - https://doi.org/10.1038/s41467-023-35798-5
M3 - Article
C2 - 36635304
SN - 2041-1723
VL - 14
SP - 173
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 173
ER -