The overall objective in this study is to determine the effects of 5 days treatment with prednisone (0.5 mg/kg/24h) on muscle protein synthesis and breakdown and to assess the concordance of the arteriovenous model using (1,2,-13C) leucine and 15Nphenylalanine with the multi-compartment model to study protein synthesis and breakdown in human subjects. These objectives can be accomplished by measurements of the enrichments of the amino acid tracers in different compartments such as plasma, extra- and intracellular fluid and muscle tRNA. Thus, arteriovenous studies over the leg will be performed in 10 healthy subjects. The studies will be repeated twice after an overnight fast, after 5 days of oral treatment with prednisone 0.5 mg/kd/day or placebo. A randomized, cross-over design will be used, with a period of 4-6 weeks between the measurements to avoid carry-over effects. Muscle biopsies will be taken twice (300-500g) at each study from Vastus lateralis for measurement of enrichments in muscle protein, tissue fluid and tRNA as well as mRNA expression of MHC isoforms, ATP production and mitochondrial enzymes. In addition, microdialysis from vastus lateralis will provide samples for analysis of enrichments in interstitial fluid. This study will provide novel information about the effects of prednisones on skeletal muscle protein synthesis and breakdown in healthy subjects. Furthermore, by measuring isotope enrichments in various precursor compartments and muscle proteins, the assumptions involved in the currently used arteriovenous model can be tested. This will provide important information in how to interpret previous studies using this model and will be a landmark study in determining methodological choices in the future to study protein metabolism.
Showing the most recent 10 out of 1267 publications
