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

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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 not comparable 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 did 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 to be explained by muscle hypertrophy. These findings highlight the therapeutic potential of beta2 -agonists for improving insulin sensitivity. KEY POINTS: While studies in rodents have highlighted beta2 -agonists as a means to augment insulin sensitivity, these studies utilized beta2 -agonists at doses inapplicable to humans. Herein we show that a 4-week treatment period with daily therapeutic inhalation of beta2 -agonist increases insulin-stimulated whole-body glucose disposal in young healthy lean men. This effect was associated with an increase of lean mass but not with changes in GLUT4 and hexokinase II or basal glycogen content in skeletal muscle nor GLUT4 content in abdominal adipose tissue. These findings suggest that the enhanced insulin-stimulated whole-body glucose disposal induced by a period of beta2 -agonist treatment in humans, at least in part, is attributed to muscle hypertrophy. Our observations extend findings in rodents and highlight the therapeutic potential of beta2 -agonists to enhance the capacity for glucose disposal and whole-body insulin sensitivity, providing important knowledge with potential application in insulin resistance.

Original languageEnglish
JournalThe Journal of physiology
Volume600
Issue number10
Pages (from-to)2345-2357
Number of pages13
ISSN0022-3751
DOIs
Publication statusPublished - May 2022

Bibliographical note

© 2022 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.

    Research areas

  • Adrenergic beta-2 Receptor Agonists, Glucose/pharmacology, Hexokinase/pharmacology, Humans, Hypertrophy, Insulin Resistance, Insulin/pharmacology, Muscle, Skeletal, Polyesters/pharmacology

ID: 78317240