***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND Loss of muscle mass with aging is a major public health concern . Omega-3 ( n-3 ) fatty acids stimulate protein anabolism in animals and might therefore be useful for the treatment of sarcopenia . However , the effect of omega-3 fatty acids on human protein metabolism is unknown . OBJECTIVE The objective of this study was to evaluate the effect of omega-3 fatty acid supplementation on the rate of muscle protein synthesis in older adults . DESIGN Sixteen healthy , older adults were r and omly assigned to receive either omega-3 fatty acids or corn oil for 8 wk . The rate of muscle protein synthesis and the phosphorylation of key elements of the anabolic signaling pathway were evaluated before and after supplementation during basal , postabsorptive conditions and during a hyperaminoacidemic-hyperinsulinemic clamp . RESULTS Corn oil supplementation had no effect on the muscle protein synthesis rate and the extent of anabolic signaling element phosphorylation in muscle . Omega-3 fatty acid supplementation had no effect on the basal rate of muscle protein synthesis ( mean ± SEM : 0.051 ± 0.005%/h compared with 0.053 ± 0.008%/h before and after supplementation , respectively ; P = 0.80 ) but augmented the hyperaminoacidemia-hyperinsulinemia-induced increase in the rate of muscle protein synthesis ( from 0.009 ± 0.005%/h above basal values to 0.031 ± 0.003%/h above basal values ; P < 0.01 ) , which was accompanied by greater increases in muscle mTOR(Ser2448 ) ( P = 0.08 ) and p70s6k(Thr389 ) ( P < 0.01 ) phosphorylation . CONCLUSION Omega-3 fatty acids stimulate muscle protein synthesis in older adults and may be useful for the prevention and treatment of sarcopenia . This trial was registered at clinical trials.gov as NCT00794079 Men have more muscle than women , but most studies evaluating sex differences in muscle protein metabolism have been unable to discern sexual dimorphism in basal muscle protein turnover rates in young and middle-aged adults . We hypothesized that the anabolic response to nutritional stimuli ( i.e. , amino acids and insulin ) would be greater in young/middle-aged men than women . We therefore measured the rates of muscle protein synthesis ( MPS ) in 16 healthy individuals [ 8 men and 8 women , matched for age ( mean + /- SE : 37.7 + /- 1.5 yr ) and body mass index ( 25.2 + /- 0.7 kg/m2 ) ] after an  overnight fast ( plasma insulin approximately 5 microU/ml and plasma phenylalanine approximately 60 microM ) and during a hyperinsulinemic-hyperaminoacidemic-euglycemic clamp ( plasma insulin approximately 28 microU/ml ; plasma phenylalanine approximately 110 microM ; plasma glucose approximately 5.4 mM ) . The rates of MPS were not different between men and women ( ANOVA main effect for sex ; P = 0.49 ) . During the clamp , the rate of MPS increased by approximately 50 % ( P = 0.003 ) with no difference in the increases from basal values between men and women ( + 0.019 + /- 0.004 vs. + 0.018 + /- 0.010%/h , respectively ; P = 0.93 ) . There were also no differences between men and women in the basal concentrations of muscle phosphorylated Akt(Ser473 ) , Akt(Thr308 ) , mTOR(Ser2448 ) , and p70s6k(Thr389 ) or in the hyperinsulinemia-hyperaminoacidemia-induced increases in phosphorylation of those signaling elements ( P > or = 0.25 ) . We conclude that there are no major differences in the rate of MPS and its intracellular control during basal conditions and during hyperinsulinemia-hyperaminoacidema between young and middle-aged adult men and women To determine the in vivo effect of amino acids ( AAs ) alone or in combination with insulin on splanchnic and muscle protein dynamics , we infused stable isotope tracers of AAs in 36 healthy subjects and sample d from femoral artery and vein and hepatic vein . The subjects were r and omized into six groups and were studied at baseline and during infusions of saline ( group 1 ) , insulin ( 0.5 mU. kg(-1 ) . min(-1 ) ) ( group 2 ) , insulin plus replacement of AAs ( group 3 ) insulin plus high-dose AAs ( group 4 ) , or somatostatin and baseline replacement doses of insulin , glucagon and GH plus high dose of AAs ( group 5 ) or saline ( group 6 ) . Insulin reduced muscle release of AAs mainly by inhibition of protein breakdown . Insulin also enhanced AA-induced muscle protein synthesis ( PS ) and reduced leucine transamination . The main effect of AAs on muscle was the enhancement of PS .  Insulin had no effect on protein dynamics or leucine transamination in splanchnic bed . However , AAs reduced protein breakdown and increased synthesis in splanchnic bed in a dose-dependent manner . AAs also enhanced leucine transamination in both splanchnic and muscle beds . Thus insulin 's anabolic effect was mostly on muscle , whereas AAs acted on muscle as well as on splanchnic bed . Insulin achieved anabolic effect in muscle by inhibition of protein breakdown , enhancing AA-induced PS , and reducing leucine transamination . AAs largely determined protein anabolism in splanchnic bed by stimulating PS and decreasing protein breakdown OBJECTIVE Skeletal muscle protein metabolism is resistant to the anabolic action of insulin in healthy , nondiabetic older adults . This defect is associated with impaired insulin-induced vasodilation and mTORC1 signaling . We hypothesized that , in older subjects , pharmacological restoration of insulin-induced capillary recruitment would improve the response of muscle protein synthesis and anabolism to insulin . RESEARCH DESIGN AND METHODS Twelve healthy , nondiabetic older subjects ( 71 ± 2 years ) were r and omized to two groups . Subjects were studied at baseline and during local infusion in one leg of insulin alone ( Control ) or insulin plus sodium nitroprusside ( SNP ) at variable rate to double leg blood flow . We measured leg blood flow by dye dilution ; muscle microvascular perfusion with contrast enhanced ultrasound ; Akt/mTORC1 signaling by Western blotting ; and muscle protein synthesis , amino acid , and glucose kinetics using stable isotope method ologies . RESULTS There were no baseline differences between groups . Blood flow , muscle perfusion , phenylalanine delivery to the leg , and intracellular availability of phenylalanine increased significantly ( P < 0.05 ) in SNP only . Akt phosphorylation increased in both groups but increased more in SNP ( P < 0.05 ) . Muscle protein synthesis and net balance ( nmol · min−1 · 100 ml · leg−1 ) increased significantly ( P < 0.05 ) in SNP ( synthesis , 43 ± 6 to 129 ± 25 ; net balance , −16 ± 3 to 26 ± 12 ) but not in Control ( synthesis , 41 ± 10 to 53 ± 8 ; net balance , −17 ± 3 to −2 ± 3 ) . CONCLUSIONS Pharmacological enhancement of muscle perfusion and amino acid availability during hyperinsulinemia improves the muscle protein anabolic  effect of insulin in older adults To define the mechanism of insulin 's anticatabolic action , the effects of three different dosages of insulin ( 0.25 , 0.5 , and 1.0 mU x kg(-1 ) x min(-1 ) ) versus saline on protein dynamics across splanchnic and skeletal muscle ( leg ) beds were determined using stable isotopes of phenylalanine , tyrosine , and leucine in 24 healthy subjects . After an overnight fast , protein breakdown in muscle exceeded protein synthesis , causing a net release of amino acids from muscle bed , while in the splanchnic bed protein synthesis exceeded protein breakdown , result ing in a net uptake of these amino acids . Insulin decreased ( P < 0.003 ) muscle protein breakdown in a dose-dependent manner with no effect on muscle protein synthesis , thus decreasing the net amino acid release from the muscle bed . In contrast , insulin decreased protein synthesis ( P < 0.03 ) in the splanchnic region with no effect on protein breakdown , thereby decreasing the net uptake of the amino acids . In addition , insulin also decreased ( P < 0.001 ) leucine nitrogen flux substantially more than leucine carbon flux , indicating increased leucine transamination ( an important biochemical process for nitrogen transfer between amino acids and across the organs ) , in a dose-dependent manner , with the magnitude of effect being greater on skeletal muscle than on the splanchnic bed . In conclusion , muscle is in a catabolic state in human subjects after an overnight fast and provides amino acids for synthesis of essential proteins in the splanchnic bed . Insulin achieves amino acid balance across splanchnic and skeletal muscle beds through its differential effects on protein dynamics in these tissue beds We have determined the individual and combined effects of insulin and prior exercise on leg muscle protein synthesis and degradation , amino acid transport , glucose uptake , and alanine metabolism .  Normal volunteers were studied in the postabsorptive state at rest and about 3 h after a heavy leg resistance exercise routine . The leg arteriovenous balance technique was used in combination with stable isotopic tracers of amino acids and biopsies of the vastus lateralis muscle . Insulin was infused into a femoral artery to increase the leg insulin concentrations to high physiologic levels without substantively affecting the whole-body level . Protein synthesis and degradation were determined as rates of intramuscular phenylalanine utilization and appearance , and muscle fractional synthetic rate ( FSR ) was also determined . Leg blood flow was greater after exercise than at rest ( P<0.05 ) . Insulin  accelerated blood flow at rest but not after exercise ( P<0.05 ) . The rates of protein synthesis and degradation were greater during the postexercise recovery ( 65+/-10 and 74+/-10 nmol x min(-1 ) x 100 ml(-1 ) leg volume , respectively ) than at rest ( 30+/-7 and 46+/-8 nmol x min(-1 ) x 100 ml(-1 ) leg volume , respectively ; P<0.05 ) . Insulin infusion increased protein synthesis at rest ( 51+/-4 nmol x min(-1 ) x 100 ml(-1 ) leg volume ) but not during the postexercise recovery ( 64+/-9 nmol x min(-1 ) x 100 ml(-1 ) leg volume ; P<0.05 ) . Insulin infusion at rest did not change the rate of protein degradation ( 48+/-3 nmol x min(-1 ) 100 ml(-1 ) leg volume ) . In contrast , insulin infusion after exercise significantly decreased the rate of protein degradation ( 52+/-9 nmol x min(-1 ) x 100 ml(-1 ) leg volume ) . The  insulin stimulatory effects on inward alanine transport and glucose uptake were three times greater during the postexercise recovery than at rest ( P<0.05 ) . In contrast , the insulin  effects on phenylalanine , leucine , and lysine transport were similar at rest and after exercise . In conclusion , the ability of insulin to stimulate glucose uptake and alanine transport and to suppress protein degradation in skeletal muscle is increased after resistance exercise . Decreased amino acid availability may limit the stimulatory effect of insulin on muscle protein synthesis after exercise We have investigated the mechanisms of the anabolic effect of insulin on muscle protein metabolism in healthy volunteers , using stable isotopic tracers of amino acids . Calculations of muscle protein synthesis , breakdown , and amino acid transport were based on data obtained with the leg arteriovenous catheterization and muscle biopsy . Insulin was infused ( 0.15 mU/min per 100 ml leg ) into the femoral artery to increase femoral venous insulin concentration ( from 10 + /- 2 to 77 + /- 9 microU/ml ) with minimal systemic perturbations . Tissue concentrations of free essential amino acids decreased ( P < 0.05 ) after insulin . The fractional synthesis rate of muscle protein ( precursor-product approach ) increased ( P < 0.01 ) after insulin from 0.0401 + /- 0.0072 to 0.0677 + /- 0.0101%/h . Consistent with this observation , rates of utilization for protein synthesis of intracellular phenylalanine and lysine ( arteriovenous balance approach ) also increased from 40 + /- 8 to 59 + /- 8 ( P < 0.05 ) and from 2 
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CONCLUSIONS From the presented data in the current systematic review , we conclude that : i ) exogenous insulin and amino acid administration effectively increase muscle protein synthesis , but this effect is attributed to the hyperaminoacidemia ; ii ) exogenous insulin administered systemically induces hypoaminoacidemia which obviates any insulin-stimulatory effect on muscle protein synthesis ; iii ) exogenous insulin result ing in supraphysiological insulin levels exceeding 50 , 000 pmol/l may effectively augment muscle protein synthesis ; iv ) exogenous insulin may have a diminished effect on muscle protein synthesis in older adults due to age-related anabolic resistance ; and v ) exogenous insulin administered systemically does not increase muscle protein synthesis in healthy , young adults