Dataset Information

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 β₂-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 [¹⁴C]deoxy-D-glucose, oxydation of [¹⁴C]glucose and [¹⁴C]oleic acid were measured. Incorporation of [¹⁴C]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 β₂-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.

SUBMITTER: Skagen C

PROVIDER: S-EPMC8663959 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Publications

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

Skagen Christine C Nyman Tuula A TA Peng Xiao-Rong XR O'Mahony Gavin G Kase Eili Tranheim ET Rustan Arild Chr AC Thoresen G Hege GH

Current research in pharmacology and drug discovery 20210611

<h4>Objective</h4><i>In vivo</i> 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 <i>in vivo</i>, the <i>in vitro</i> data are limited to mouse and rat cell lines. Therefore, we sought to discover the effects of the β<sub>2</sub>-adrenergic receptor agonist terbutaline on me ...[more]

PMID: 34909668

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Project description:Aims/hypothesisHypoglycaemia is a major barrier to good glucose control in type 1 diabetes. Frequent hypoglycaemic episodes impair awareness of subsequent hypoglycaemic bouts. Neural changes underpinning awareness of hypoglycaemia are poorly defined and molecular mechanisms by which glial cells contribute to hypoglycaemia sensing and glucose counterregulation require further investigation. The aim of the current study was to examine whether, and by what mechanism, human primary astrocyte (HPA) function was altered by acute and recurrent low glucose (RLG).MethodsTo test whether glia, specifically astrocytes, could detect changes in glucose, we utilised HPA and U373 astrocytoma cells and exposed them to RLG in vitro. This allowed measurement, with high specificity and sensitivity, of RLG-associated changes in cellular metabolism. We examined changes in protein phosphorylation/expression using western blotting. Metabolic function was assessed using a Seahorse extracellular flux analyser. Immunofluorescent imaging was used to examine cell morphology and enzymatic assays were used to measure lactate release, glycogen content, intracellular ATP and nucleotide ratios.ResultsAMP-activated protein kinase (AMPK) was activated over a pathophysiologically relevant glucose concentration range. RLG produced an increased dependency on fatty acid oxidation for basal mitochondrial metabolism and exhibited hallmarks of mitochondrial stress, including increased proton leak and reduced coupling efficiency. Relative to glucose availability, lactate release increased during low glucose but this was not modified by RLG. Basal glucose uptake was not modified by RLG and glycogen levels were similar in control and RLG-treated cells. Mitochondrial adaptations to RLG were partially recovered by maintaining euglycaemic levels of glucose following RLG exposure.Conclusions/interpretationTaken together, these data indicate that HPA mitochondria are altered following RLG, with a metabolic switch towards increased fatty acid oxidation, suggesting glial adaptations to RLG involve altered mitochondrial metabolism that could contribute to defective glucose counterregulation to hypoglycaemia in diabetes.

Dataset Information

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

Objective

Methods

Results

Conclusion

Publications

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

Similar Datasets

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