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

OBJECTIVE

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 , the data are limited to mouse and rat cell lines. Therefore, we sought to discover the effects of the β-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 [C]deoxy-D-glucose, oxydation of [C]glucose and [C]oleic acid were measured. Incorporation of [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-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.