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 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.
|Tidsskrift||Journal of Physiology|
|Status||Udgivet - 2022|
CURIS 2022 NEXS 083
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