Chronic treatment with terbutaline increases glucose and oleic acid oxidation and protein synthesis in cultured human myotubes

Abstract

Objective In vivo studies have reported several beneficial metabolic effects of β-adrenergic receptor agonist administration in skeletal muscle, including increased glucose uptake, fatty acid metabolism, lipolysis and mitochondrial biogenesis. Although these effects have been widely studied in vivo , the in vitro data are limited to mouse and rat cell lines. Therefore, we sought to discover the effects of the β 2 -adrenergic receptor agonist terbutaline on metabolism and protein synthesis in human primary skeletal muscle cells. Methods Human cultured myotubes were exposed to terbutaline in various concentrations (0.01–30 ​μM) for 4 or 96 ​h. Thereafter uptake of [ 14 C]deoxy-D-glucose, oxydation of [ 14 C]glucose and [ 14 C]oleic acid were measured. Incorporation of [ 14 C]leucine, gene expression by qPCR and proteomics analyses by mass spectrometry by the STAGE-TIP method were performed after 96 ​h exposure to 1 and 10 ​μM of terbutaline. Results The results showed that 4 ​h treatment with terbutaline in concentrations up to 1 ​μM increased glucose uptake in human myotubes, but also decreased both glucose and oleic acid oxidation along with oleic acid uptake in concentrations of 10–30 ​μM. Moreover, administration of terbutaline for 96 ​h increased glucose uptake (in terbutaline concentrations up to 1 ​μM) and oxidation (1 ​μM), as well as oleic acid oxidation (0.1–30 ​μM), leucine incorporation into cellular protein (1–10 ​μM) and upregulated several pathways related to mitochondrial metabolism (1 ​μM). Data are available via ProteomeXchange with identifier PXD024063. Conclusion These results suggest that β 2 -adrenergic receptor have direct effects in human skeletal muscle affecting fuel metabolism and net protein synthesis, effects that might be favourable for both type 2 diabetes and muscle wasting disorders.

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

“…2019; Skagen et al . 2021) and clinical trials aiming to assess the applicability of selective beta 2 ‐agonists in lifestyle diseases such as obesity and type 2 diabetes, as well as muscle atrophic conditions (patent no: WO2005072714A1, ClinicalTrials.gov Identifier: NCT03005717.23‐25).…”

“…These effects include muscle growth (Hostrup et al 2015;Jessen et al 2018), slow-to-fast twitch muscle fibre type transition (Hostrup et al 2018a), lipolysis (Onslev et al 2019), and alterations of numerous proteins involved in cellular metabolism (Hostrup et al 2018a,b). This has made the beta 2 -adrenergic receptor an emerging area in pharmaceutical drug development, with ongoing pre-clinical (Koziczak-Holbro et al 2019;Skagen et al 2021) and clinical trials aiming to assess the applicability of selective beta 2 -agonists in lifestyle diseases such as obesity and type 2 diabetes, as well as muscle atrophic conditions (patent no: WO2005072714A1, ClinicalTrials.gov Identifier: NCT03005717. [23][24][25].…”

Effect of noradrenaline on propofol-induced mitochondrial dysfunction in human skeletal muscle cells

“…Firstly, noradrenaline increased mitochondrial network mass and size, most likely by increased mitochondrial turnover, as evidenced by increased mitophagy. Several studies have found that catecholamine-induced stimulation of β-adrenergic receptors promotes mitochondrial biogenesis in both skeletal muscle [ 32 , 33 ] and other tissues [ 34 , 35 ]. In keeping with this, noradrenaline significantly increased mitochondrial content what we confirmed by three independent techniques.…”