RESUMEN
OBJECTIVE: In vivo studies have reported several beneficial metabolic effects of ß-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 ß2-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 âµM) for 4 or 96 âh. 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 âh exposure to 1 and 10 âµM of terbutaline. RESULTS: The results showed that 4 âh treatment with terbutaline in concentrations up to 1 âµM 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 âµM. Moreover, administration of terbutaline for 96 âh increased glucose uptake (in terbutaline concentrations up to 1 âµM) and oxidation (1 âµM), as well as oleic acid oxidation (0.1-30 âµM), leucine incorporation into cellular protein (1-10 âµM) and upregulated several pathways related to mitochondrial metabolism (1 âµM). Data are available via ProteomeXchange with identifier PXD024063. CONCLUSION: These results suggest that ß2-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.
RESUMEN
The objective of the study was to evaluate potential benefits of docosahexaenoic acid (DHA) rich fish oil supplementation as an adjunct to statin therapy for hyperlipidaemia. A total of 45 hyperlipidaemic patients on stable statin therapy with persistent elevation of plasma triglycerides (averaging 2.2 mmol/L) were randomised to take 4 g/day (n = 15) or 8 g/day (n = 15) of tuna oil or olive oil (placebo, n = 15) for 6 months. Plasma lipids, blood pressure and arterial compliance were assessed initially and after 3 and 6 months in 40 subjects who completed the trial. Plasma triglycerides were reduced 27% by 8 g/day DHA-rich fish oil (P < 0.05) but not by 4 g/day when compared with the placebo and this reduction was achieved by 3 months and was sustained at 6 months. Even though total cholesterol was already well controlled by the statin treatment (mean initial level 4.5 mmol/L), there was a further dose-dependent reduction with fish oil supplementation (r = -0.344, P < 0.05). The extent of total cholesterol reduction correlated (r = -0.44) with the initial total cholesterol levels (P < 0.005). In the subset with initial plasma cholesterol above 3.8 mmol/L, plasma very low density lipoprotein (VLDL), intermediate-density lipoprotein (IDL) and low-density lipoprotein (LDL) were isolated and assayed for cholesterol and apolipoprotein B (apoB) at the commencement of the trial and at 3 months of intervention. Fish oil tended to lower cholesterol and apoB in VLDL and raise both in LDL. There were no changes in IDL cholesterol, IDL apoB and high-density lipoprotein cholesterol. The results demonstrate that DHA-rich fish oil supplementation (2.16 g DHA/day) can improve plasma lipids in a dose-dependent manner in patients taking statins and these changes were achieved by 3 months. Fish oil in addition to statin therapy may be preferable to drug combinations for the treatment of combined hyperlipidaemia.
Asunto(s)
Ácidos Docosahexaenoicos/uso terapéutico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Hiperlipidemias/tratamiento farmacológico , Lípidos/sangre , Animales , Apolipoproteínas B/sangre , Atorvastatina , LDL-Colesterol/sangre , Grasas de la Dieta/administración & dosificación , Grasas de la Dieta/uso terapéutico , Grasas Insaturadas en la Dieta/sangre , Suplementos Dietéticos , Ácidos Docosahexaenoicos/administración & dosificación , Relación Dosis-Respuesta a Droga , Ácidos Grasos Monoinsaturados/uso terapéutico , Femenino , Aceites de Pescado/administración & dosificación , Aceites de Pescado/uso terapéutico , Fluvastatina , Ácidos Heptanoicos/uso terapéutico , Humanos , Hiperlipidemias/sangre , Indoles/uso terapéutico , Metabolismo de los Lípidos/efectos de los fármacos , Lipoproteínas IDL/sangre , Lipoproteínas VLDL/sangre , Masculino , Persona de Mediana Edad , Piridinas/uso terapéutico , Pirroles/uso terapéutico , Simvastatina/uso terapéutico , Resultado del Tratamiento , Triglicéridos/sangreRESUMEN
Myoblasts from human skeletal muscle were isolated from needle biopsy samples of the vastus lateralis of young and healthy volunteers. Contaminating fibroblasts were removed, and myoblasts were fused into differentiated multinucleated myotubes. These myotubes manifested both basal and insulin-stimulated (1-100 nM) glucose transport and glycogen synthesis. Insulin increased 2-deoxyglucose uptake by 1.4-fold and glycogen synthesis by 2.1-fold. Measurements of impedance of cell-covered gold electrodes (ECIS system) showed increased micromotion of caffeine-stimulated cells, showing their ability to contract. Acute electrical stimulation of the myotubes increased 2-deoxyglucose uptake by about 30%. Treatment with high glucose concentrations (10-20 mM) for 2-8 days reduced both basal and insulin-stimulated glucose uptake. Maximal effect was seen after 2 days of treatment with 20 mM glucose. Baseline glucose uptake and glycogen synthesis were reduced by 35%, insulin-stimulated glucose uptake by 25%, and insulin-stimulated glycogen synthesis by 39%. Total cell content of glycogen was not changed by hyperglycemia. The insulin-stimulated glucose uptake in hyperglycemia-treated cells was improved by electrical stimulation of the cells. In conclusion, a model of hyperglycemia has been established, and electrical stimulation improved insulin responses.