Pharmacological and genetic approaches to modulate energy metabolism in skeletal muscle cells
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- Farmasøytisk institutt [1934]
Abstract
The prevalence of obesity and related metabolic illnesses have rapidly increased over the last decades. One of these diseases is type 2 diabetes (T2D), characterized by chronic hyperglycaemia and insulin resistance in several organs including skeletal muscle, an organ of particular interest when it comes to further understand metabolic conditions. In this thesis, we aimed to study the effects of different pharmacological and genetic approaches on skeletal muscle energy metabolism. The results presented in this thesis shows that activation of β2-adrenergic receptors and the cold-sensing transient receptor potential ion channels (TRP), inhibiting diacylglycerol acyltransferase (DGAT) and ablation of the α2 subunit of adenosine 5’-monophosphate (AMP)-activated protein kinase (AMPK) affected energy metabolism in myotubes. The β2- agonist terbutaline increased glucose uptake, glucose and fatty acid oxidation, upregulated mitochondrial and oxidative pathways and increased protein synthesis. Activation of TRPA1 resulted in an increased glucose uptake and oxidation, whereas inhibiting of DGAT and ablation of α2 subunit of AMPK resulted in alterations in lipid metabolism.List of papers
Paper I. Skagen C, Nyman TA, Peng XR, O’Mahony G, Kase ET, Rustan AC, Thoresen GH. Chronic treatment with terbutaline increases glucose and oleic acid oxidation and protein synthesis in cultured human myotubes CRPHAR. 2021 Jun 11;2:100039. DOI: 10.1016/j.crphar.2021.100039. The article is included in the thesis. Also available at: https://doi.org/10.1016/j.crphar.2021.100039 |
Paper II. Skagen C, Løvsletten NG, Asoawe L, Al-Karbawi Z, Rustan AC, Thoresen GH, Haugen F. Expression and metabolic functions of the thermally activated transient receptor potential channels TRPA1 and TRPM8 in human myotubes. Submitted to Journal of Thermal Biology. To be published. The paper is not available in DUO awaiting publishing. |
Paper III. Løvsletten NG, Vu H, Skagen C, Lund J, Kase ET, Thoresen GH, Zammit VA, Rustan AC. Treatment of human skeletal muscle cells with inhibitors of diacylglycerol acyltransferases 1 and 2 to explore isozyme-specific roles on lipid metabolism. Sci Rep. 2020;10(1):238. DOI: 10.1038/s41598-019-57157-5. The article is included in the thesis. Also available at: https://doi.org/10.1038/s41598-019-57157-5 |
Paper IV. Skagen C, Nyman TA, Janovska P, Horakova O, Kopecky J, Rustan AC, Thoresen GH. Loss of AMPKα2 increases substrate oxidation, but decreases relative maximal oxidative capacity and incorporation of exogenous fatty acids into lipids in cultured myotubes. Manuscript. To be published. The paper is not available in DUO awaiting publishing. |