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

Abstract

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Improving skeletal muscle insulin sensitivity via beta2‐agonist administration: a promising strategy to counteract metabolic disease and muscle loss

“…preferential oxidation of glucose over fat and glycogen accumulation; Scheidegger et al., 1984) likely explain part of the increase in glucose disposal. Although Jessen and colleagues did not observe changes in protein content of GLUT4 or hexokinase in muscle tissue (Jessen et al., 2022), previous work has proposed that these effects are (at least in part) mediated via activation of a novel beta 2 ‐adrenoceptor signalling pathway (Sato et al., 2014). This pathway leads to GLUT4 translocation via mammalian target of rapamycin complex 2 phosphorylation, largely independently from the phosphoinositide 3‐kinase–Akt signalling pathway.…”

“…Because of the demonstrated hypertrophic and insulin-sensitising effects, beta 2 -agonists treatment is a promising strategy in conditions characterised by muscle atrophy and insulin resistance. To illustrate the potency of chronic beta 2 -agonist treatment, the measured 25% difference between the terbutaline and placebo groups (Jessen et al, 2022) is of similar magnitude to the difference between glucose-tolerant individuals and individuals with type 2 diabetes, and equivalent to the decline observed following 30-40 years of ageing, and may therefore be able to (partly) overcome the observed metabolic Perspective J Physiol 600.10 deterioration in these conditions. Moreover, given the concomitant stimulatory effect on both muscle mass and insulin sensitivity, the administration of short-acting beta 2 -agonists during periods of limb immobilisation or bed rest is a highly promising approach to attenuate or even prevent muscle disuse-induced atrophy and insulin resistance (Dirks et al, 2020).…”

“…In this issue of The Journal of Physiology , Jessen and co‐workers publish novel work using chronic beta 2 ‐agonist administration at therapeutic doses to improve insulin sensitivity in healthy young men (Jessen et al., 2022). The authors conducted a thoroughly controlled human intervention study to assess the impact of daily inhalation of the selective beta 2 ‐agonist terbutaline on insulin‐stimulated whole‐body glucose disposal and potentially relevant physiological mechanisms in both skeletal muscle and adipose tissue.…”

“…The improvement in insulin sensitivity was accompanied by a favourable change in body composition, characterised by a 1.1 kg increase in lean mass and concomitant 0.5 kg fat mass loss. Skeletal muscle is the major site for insulin‐stimulated glucose uptake, with >80% of glucose disposal occurring in muscle under these hyperinsulinaemic–euglycaemic conditions (Jessen et al., 2022). Indeed, the authors demonstrate that the observed changes in lean mass are strongly correlated with the improvements in insulin‐stimulated glucose uptake, suggesting that the positive effects of chronic beta 2 ‐agonist administration on insulin sensitivity are, potentially in large part, attributable to muscle hypertrophy.…”

Mechanisms of cold-induced improvements in glucose homeostasis

“…At thermoneutrality (30˚C), rodent WAT contains relatively large lipid droplets, few mitochondria and is (almost completely) deprived of UCP1 expression (50,(52)(53)(54).…”