Insulin facilitation of muscle protein synthesis following resistance exercise in hindlimb-suspended rats is independent of a rapamycinsensitive pathway. 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

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... muscle hypertrophy stimulant, on rates of protein synthesis after 4 days of HS in mature male Sprague-Dawley rats. Flywheel resistance exercise (2 sets ϫ 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 Ͻ 0.05) with HS, but this loss of mass was not observed (P Ͼ 0.05) with HSRE. Muscle protein synthesis was diminished (P Ͻ 0.05) with HS, with or without insulin. HSRE also had reduced rates of synthesis without insulin; however, insulin administration yielded higher (P Ͻ 0.05) rates in HSRE compared with HS or control. Rapamycin diminished protein synthesis in all groups (P Ͻ 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 RODENT HINDLIMB SUSPENSION has been used as a ground-based model for studying musculoskeletal changes that occur during space flight (3, 6 -8, 19 -21, 26, 27, 34) and disuse because of comparable decreases in the size of selected hindlimb muscles (1, 6, 7, 25, 27) . The soleus muscle, predominately composed of slow-twitch fibers, atrophies to the greatest extent with hindlimb unloading, which is due, in part, to a reduction of muscle protein synthesis (12, 30). Mechanisms associated with this reduction of muscle protein synthesis are not completely understood but may involve alterations of signaling controlling the mRNA translational process.