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Articles by K. E Yarasheski
Total Records ( 2 ) for K. E Yarasheski
  J. E Stevens Lapsley , F Ye , M Liu , S. E Borst , C Conover , K. E Yarasheski , G. A Walter , H. L Sweeney and K. Vandenborne

Insulin-like growth factor I (IGF-I) is a potent myogenic factor that plays a critical role in muscle regeneration and muscle hypertrophy. The purpose of this study was to evaluate the effect of IGF-I overexpression on the recovery of muscle size and function during reloading/reambulation after a period of cast immobilization in predominantly fast twitch muscles. In addition, we investigated concomitant molecular responses in IGF-I receptor and binding proteins (BPs). Recombinant adeno-associated virus vector for IGF-I (rAAV-IGF-IA) was injected into the anterior compartment of one of the hindlimbs of young (3 wk) C57BL6 female mice. At 20 wk of age, both hindlimbs were cast immobilized in a shortened position for 2 wk to unload the tibialis anterior (TA) and extensor longus digitorum (EDL) muscles. The TA and EDL muscles were removed bilaterally after 2 wk of cast immobilization and after 1 and 3 wk of free cage reambulation. Increases in IGF-I mRNA and protein levels with IGF-I overexpression were associated with significant increases in muscle wet weight, fiber size, and tetanic force, although overexpression did not protect against cast immobilization-induced muscle atrophy. After 1 wk of reambulation, evidence of enhanced muscle regeneration was noted in IGF-I-overexpressing muscles with an increased prevalence of central nuclei, embryonic myosin, and Pax7 positive fibers. We also observed larger relative gains in muscle size (wet weight and fiber area), but not force, during the 3-wk reambulation period in hindlimb muscles overexpressing IGF-I compared with contralateral control legs. Changes in IGFBP-5 mRNA expression during cast immobilization and reambulation paralleled those of IGF-I, whereas IGFBP-3 expression changed inversely to IGFBP-5.

  F. R Sattler , C Castaneda Sceppa , E. F Binder , E. T Schroeder , Y Wang , S Bhasin , M Kawakubo , Y Stewart , K. E Yarasheski , J Ulloor , P Colletti , R Roubenoff and S. P. Azen

Context: Impairments in the pituitary-gonadal axis with aging are associated with loss of muscle mass and function and accumulation of upper body fat.

Objectives: We tested the hypothesis that physiological supplementation with testosterone and GH together improves body composition and muscle performance in older men.

Design, Setting, and Participants: One hundred twenty-two community-dwelling men 70.8 ± 4.2 yr of age with body mass index of 27.4 ± 3.4 kg/m2, testosterone of 550 ng/dl or less, and IGF-I in lower adult tertile (≤167 ng/dl) were randomized to receive transdermal testosterone (5 or 10 g/d) during a Leydig cell clamp plus GH (0, 3, or 5 µg/kg · d) for 16 wk.

Main Outcome Measures: Body composition by dual-energy x-ray absorptiometry, muscle performance, and safety tests were conducted.

Results: Total lean body mass increased (1.0 ± 1.7 to 3.0 ± 2.2 kg) as did appendicular lean tissue (0.4 ± 1.4 to 1.5 ± 1.3 kg), whereas total fat mass decreased by 0.4 ± 0.9 to 2.3 ± 1.7 kg as did trunk fat (0.5 ± 0.9 to 1.5 ± 1.0 kg) across the six treatment groups and by dose levels for each parameter (P ≤ 0.0004 for linear trend). Composite maximum voluntary strength of upper and lower body muscles increased by 14 ± 34 to 35 ± 31% (P < 0.003 in the three highest dose groups) that correlated with changes in appendicular lean mass. Aerobic endurance increased in all six groups (average 96 ± 137sec longer). Systolic and diastolic blood pressure increased similarly in each group with mean increases of 12 ± 14 and 8 ± 8 mm Hg, respectively. Other predictable adverse events were modest and reversible.

Conclusions: Supplemental testosterone produced significant gains in total and appendicular lean mass, muscle strength, and aerobic endurance with significant reductions in whole-body and trunk fat. Outcomes appeared to be further enhanced with GH supplementation.

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