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.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
General Clinical Research Centers Program (M01)
Project #
2M01RR000585-29
Application #
6409742
Study Section
National Center for Research Resources Initial Review Group (RIRG)
Project Start
1976-12-01
Project End
2004-11-30
Budget Start
Budget End
Support Year
29
Fiscal Year
2000
Total Cost
Indirect Cost
Name
Mayo Clinic, Rochester
Department
Type
DUNS #
City
Rochester
State
MN
Country
United States
Zip Code
55905
Dad, Taimur; Abebe, Kaleab Z; Bae, K Ty et al. (2018) Longitudinal Assessment of Left Ventricular Mass in Autosomal Dominant Polycystic Kidney Disease. Kidney Int Rep 3:619-624
Yu, Alan S L; Shen, Chengli; Landsittel, Douglas P et al. (2018) Baseline total kidney volume and the rate of kidney growth are associated with chronic kidney disease progression in Autosomal Dominant Polycystic Kidney Disease. Kidney Int 93:691-699
Kamimura, Daisuke; Suzuki, Takeki; Wang, Wanmei et al. (2018) Higher plasma leptin levels are associated with reduced left ventricular mass and left ventricular diastolic stiffness in black women: insights from the Genetic Epidemiology Network of Arteriopathy (GENOA) study. Hypertens Res 41:629-638
Nowak, Kristen L; You, Zhiying; Gitomer, Berenice et al. (2018) Overweight and Obesity Are Predictors of Progression in Early Autosomal Dominant Polycystic Kidney Disease. J Am Soc Nephrol 29:571-578
Tirumanisetty, P; Prichard, D; Fletcher, J G et al. (2018) Normal values for assessment of anal sphincter morphology, anorectal motion, and pelvic organ prolapse with MRI in healthy women. Neurogastroenterol Motil 30:e13314
McKenzie, Katelyn A; El Ters, Mirelle; Torres, Vicente E et al. (2018) Relationship between caffeine intake and autosomal dominant polycystic kidney disease progression: a retrospective analysis using the CRISP cohort. BMC Nephrol 19:378
Brosnahan, Godela M; Abebe, Kaleab Z; Rahbari-Oskoui, Frederic F et al. (2017) Effect of Statin Therapy on the Progression of Autosomal Dominant Polycystic Kidney Disease. A Secondary Analysis of the HALT PKD Trials. Curr Hypertens Rev 13:109-120
Kamimura, Daisuke; Suzuki, Takeki; Furniss, Anna L et al. (2017) Elevated serum osteoprotegerin is associated with increased left ventricular mass index and myocardial stiffness. J Cardiovasc Med (Hagerstown) 18:954-961
Chung, Jin Ook; Koutsari, Christina; Blachnio-Zabielska, Agnieszka U et al. (2017) Intramyocellular Ceramides: Subcellular Concentrations and Fractional De Novo Synthesis in Postabsorptive Humans. Diabetes 66:2082-2091
West, Nancy A; Lirette, Seth T; Cannon, Victoria A et al. (2017) Adiposity, Change in Adiposity, and Cognitive Decline in Mid- and Late Life. J Am Geriatr Soc 65:1282-1288

Showing the most recent 10 out of 1267 publications