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dc.identifier.citationRønning, Camilla. Studies on physiological and intracellular effects of moxonidine in human skeletal muscle cells. Hovedoppgave, University of Oslo, 2006en_US
dc.description.abstractThe sympatholytic antihypertensive agent moxonidine, a centrally-acting I1-imidazoline receptor agonist, has in clinical studies shown a beneficial effect on insulin resistance in hypertensive patients. Since skeletal muscle is the major organ involved in glucose disposal, experiments were performed to investigate whether moxonidine have direct effects on skeletal muscle cells in vitro. Satellite cells from skeletal muscle biopsies (musculus vastus lateralis and musculus transversus abdominis) were differentiated into myotubes and stimulated with moxonidine. Studies of glucose uptake was performed with [2-3H]-deoxyglucose. Further, the specificity of the glucose transport was explored by applying cytochalasin B, an inhibitor of glucose transporters. The intracellular signalling mechanism of moxonidine was investigated with Western blotting using antibodies against the intracellular kinases Akt and ERK, and the glucose transporter GLUT-4, respectively. Expression of GLUT-4 was also measured by real-time PCR. The involvement of Gi-protein-coupling in the signalling pathway of moxonidine was examined by adding pertussis toxin prior to moxonidine-incubation. Moxonidine treatment for 60 minutes yielded a minor increase in glucose uptake of skeletal muscle cells, with a maximum increase of 31 % by 3 nM moxonidine. This confirms the beneficial effects on glucose metabolism seen in clinical studies. Moxonidine treatment for 15 minutes tended to increase the phosphorylation of Akt, yielding a maximum increase of 41 %. Experiments with perussis toxin did not indicate that Gi-coupling is involved in the intracellular signalling of moxonidine. In the literature, studies report the activation of ERK by moxonidine. However, ERK does not seem to be involved in the signalling mechanism of moxonidine in our cell model. The expression of GLUT-4 protein was significantly increased with a maximum of 70 % after 72 hours of moxonidine treatment, however, only a small increase in the level of GLUT-4 mRNA was detected. The activation of Akt and the increase seen in GLUT-4 protein might be involved in the mechanism behind the metabolic effects of moxonidine.nor
dc.subjectfarmakologi imidazoline reseptor glukose opptak Akt ERK GLUT-4 intracellular signaleringen_US
dc.titleStudies on physiological and intracellular effects of moxonidine in human skeletal muscle cellsen_US
dc.typeMaster thesisen_US
dc.creator.authorRønning, Camillaen_US
dc.identifier.bibliographiccitationinfo:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&rft.au=Rønning, Camilla&rft.title=Studies on physiological and intracellular effects of moxonidine in human skeletal muscle cells&rft.inst=University of Oslo&rft.date=2006&rft.degree=Hovedoppgaveen_US
dc.contributor.supervisorRigmor Solberg og Hege Thoresenen_US

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