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Am J Physiol Endocrinol Metab 287: E1070-E1075, 2004. First published August 10, 2004; doi:10.1152/ajpendo.00329.2004
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Insulin facilitation of muscle protein synthesis following resistance exercise in hindlimb-suspended rats is independent of a rapamycin-sensitive pathway

James D. Fluckey,1,2 Esther E. Dupont-Versteegden,1,2 Micheal Knox,2 Dana Gaddy,2 Per A. Tesch,3 and Charlotte A. Peterson1,2,4

Departments of 1Geriatrics and 2Physiology and Biophysics, University of Arkansas for Medical Sciences, and the 4Central Arkansas Veterans Health Care System, Little Rock, Arkansas 72205; and 3Karolinska Institute, S-171 77 Stockholm, Sweden

Submitted 26 July 2004 ; accepted in final form 6 August 2004

Hindlimb suspension (HS) results in rapid losses of muscle mass, which may in part be explained by attenuated rates of protein synthesis. Mammalian target of rapamycin (mTOR) regulates protein synthesis and has been implicated as a potential mediator of the muscle mass decrement with HS. This study examined the effect of resistance exercise, a muscle hypertrophy stimulant, on rates of protein synthesis after 4 days of HS in mature male Sprague-Dawley rats. Flywheel resistance exercise (2 sets x 25 repetitions) was conducted on days 2 and 4 of HS (HSRE). Sixteen hours after the last exercise bout, soleus muscles were assessed for in vitro rates of protein synthesis, with and without insulin (signaling agonist) and/or rapamycin (mTOR inhibitor). Results demonstrated that soleus mass was reduced (P < 0.05) with HS, but this loss of mass was not observed (P > 0.05) with HSRE. Muscle protein synthesis was diminished (P < 0.05) with HS, with or without insulin. HSRE also had reduced rates of synthesis without insulin; however, insulin administration yielded higher (P < 0.05) rates in HSRE compared with HS or control. Rapamycin diminished protein synthesis in all groups (P < 0.05), but insulin rescued synthesis rates in HS and HSRE to levels similar to insulin alone for each group, suggesting that alternate signaling pathways develop to increase protein synthesis with HS. These results demonstrate that the capacity for an augmented anabolic response to resistance exercise is maintained after 4 days of HS and is independent of a rapamycin-sensitive pathway.

muscle atrophy; flywheel technology; phenylalanine; mammalian target of rapamycin; microgravity



Address for reprint requests and other correspondence: J. D. Fluckey, Nutrition, Metabolism and Exercise Laboratory, Univ. of Arkansas for Medical Sciences, 4301 W. Markham, Slot 806, Little Rock, AR 72205 (E-mail: Fluckeyjamesd{at}uams.edu)




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