TY - JOUR

T1 - Muscle hypertrophic effect of inhaled beta2-agonist is associated with augmented insulin-stimulated whole-body glucose disposal in young men

AU - Jessen, Søren

AU - Baasch-Skytte, Thomas

AU - Onslev, Johan

AU - Eibye, Kasper

AU - Backer, Vibeke

AU - Bangsbo, Jens

AU - Hostrup, Morten

N1 - This article is protected by copyright. All rights reserved.

PY - 2022

Y1 - 2022

N2 - Rodent studies highlight enhancement of glucose tolerance and insulin sensitivity as potential clinically relevant effects of chronic beta2-agonist treatment. However, the doses administered to rodents are incomparable with the therapeutic doses used for humans. Thus, we investigated the physiological effects of prolonged beta2-agonist treatment at inhaled doses resembling those used in respiratory diseases on insulin-stimulated whole-body glucose disposal and putative mechanisms in skeletal muscle and adipose tissue of healthy men. Utilizing a randomized placebo-controlled parallel-group design, we assigned 21 healthy men to 4 weeks daily inhalation of terbutaline (TER; 4 mg×day-1 , n = 13) or placebo (PLA, n = 8). Before and after treatments, we assessed subjects' whole-body insulin-stimulated glucose disposal and body composition, and collected vastus lateralis muscle and abdominal adipose tissue biopsies. Glucose infusion rate increased by 27% (95% CI: 80 to 238 mg×min-1 , P = 0.001) in TER, whereas no significant changes occurred in PLA (95% CI: -37 to 195 mg×min-1 , P = 0.154). GLUT4 content in muscle or adipose tissue did not change nor hexokinase II content or markers of mitochondrial volume in muscle. Change in lean mass was associated with change in glucose infusion rate in TER (r = 0.59, P = 0.03). Beta2-agonist treatment in close-to-therapeutic doses may augment whole-body insulin-stimulated glucose disposal in healthy young men and part of the change is likely explained by muscle hypertrophy. These findings highlight the therapeutic potential of beta2 -agonists for improving insulin sensitivity.

AB - Rodent studies highlight enhancement of glucose tolerance and insulin sensitivity as potential clinically relevant effects of chronic beta2-agonist treatment. However, the doses administered to rodents are incomparable with the therapeutic doses used for humans. Thus, we investigated the physiological effects of prolonged beta2-agonist treatment at inhaled doses resembling those used in respiratory diseases on insulin-stimulated whole-body glucose disposal and putative mechanisms in skeletal muscle and adipose tissue of healthy men. Utilizing a randomized placebo-controlled parallel-group design, we assigned 21 healthy men to 4 weeks daily inhalation of terbutaline (TER; 4 mg×day-1 , n = 13) or placebo (PLA, n = 8). Before and after treatments, we assessed subjects' whole-body insulin-stimulated glucose disposal and body composition, and collected vastus lateralis muscle and abdominal adipose tissue biopsies. Glucose infusion rate increased by 27% (95% CI: 80 to 238 mg×min-1 , P = 0.001) in TER, whereas no significant changes occurred in PLA (95% CI: -37 to 195 mg×min-1 , P = 0.154). GLUT4 content in muscle or adipose tissue did not change nor hexokinase II content or markers of mitochondrial volume in muscle. Change in lean mass was associated with change in glucose infusion rate in TER (r = 0.59, P = 0.03). Beta2-agonist treatment in close-to-therapeutic doses may augment whole-body insulin-stimulated glucose disposal in healthy young men and part of the change is likely explained by muscle hypertrophy. These findings highlight the therapeutic potential of beta2 -agonists for improving insulin sensitivity.

KW - Faculty of Science

KW - Adrenoceptor

KW - Adrenergic

KW - Muscle hypertrophy

KW - Glucose transport

KW - Insulin sensitivity

KW - Clenbuterol

KW - Salbutamol

KW - SABA

U2 - 10.1113/JP282421

DO - 10.1113/JP282421

M3 - Journal article

C2 - 35218559

VL - 600

SP - 2345

EP - 2357

JO - The Journal of Physiology

JF - The Journal of Physiology

SN - 0022-3751

IS - 10

ER -