PMID- 15304378 OWN - NLM STAT- MEDLINE DCOM- 20041216 LR - 20211203 IS - 0193-1849 (Print) IS - 0193-1849 (Linking) VI - 287 IP - 6 DP - 2004 Dec TI - Insulin facilitation of muscle protein synthesis following resistance exercise in hindlimb-suspended rats is independent of a rapamycin-sensitive pathway. PG - E1070-5 AB - 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. FAU - Fluckey, James D AU - Fluckey JD AD - Nutrition, Metabolism and Exercise Laboratory, University of Arkansas for Medical Sciences, 4301 W. Markham, Slot 806, Little Rock, AR 72205, USA. Fluckeyjamesd@uams.edu FAU - Dupont-Versteegden, Esther E AU - Dupont-Versteegden EE FAU - Knox, Micheal AU - Knox M FAU - Gaddy, Dana AU - Gaddy D FAU - Tesch, Per A AU - Tesch PA FAU - Peterson, Charlotte A AU - Peterson CA LA - eng GR - AR 47577/AR/NIAMS NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. DEP - 20040810 PL - United States TA - Am J Physiol Endocrinol Metab JT - American journal of physiology. Endocrinology and metabolism JID - 100901226 RN - 0 (Insulin) RN - 0 (Muscle Proteins) RN - EC 2.7.- (Protein Kinases) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - W36ZG6FT64 (Sirolimus) SB - IM MH - Animals MH - *Hindlimb Suspension MH - Insulin/*pharmacology MH - Male MH - Muscle Proteins/*biosynthesis MH - Muscle, Skeletal/anatomy & histology/*physiology MH - Organ Size MH - Physical Exertion/*physiology MH - Protein Kinases/drug effects/*physiology MH - Rats MH - Rats, Sprague-Dawley MH - Sirolimus/*pharmacology MH - TOR Serine-Threonine Kinases MH - Time Factors OTO - NASA OT - Non-programmatic EDAT- 2004/08/12 05:00 MHDA- 2004/12/17 09:00 CRDT- 2004/08/12 05:00 PHST- 2004/08/12 05:00 [pubmed] PHST- 2004/12/17 09:00 [medline] PHST- 2004/08/12 05:00 [entrez] AID - 00329.2004 [pii] AID - 10.1152/ajpendo.00329.2004 [doi] PST - ppublish SO - Am J Physiol Endocrinol Metab. 2004 Dec;287(6):E1070-5. doi: 10.1152/ajpendo.00329.2004. Epub 2004 Aug 10.