Latency and duration of stimulation of human muscle protein synthesis during continuous infusion of amino acids

Abstract

1. The aim of this study was to describe the time course of the response of human muscle protein synthesis (MPS) to a square wave increase in availability of amino acids (AAs) in plasma. We investigated the responses of quadriceps MPS to a approximately 1.7-fold increase in plasma AA concentrations using an intravenous infusion of 162 mg (kg body weight)(-1) h(-1) of mixed AAs. MPS was estimated from D3-leucine labelling in protein after a primed, constant intravenous infusion of D3-ketoisocaproate, increased appropriately during AA infusion. 2. Muscle was separated into myofibrillar, sarcoplasmic and mitochondrial fractions. MPS, both of mixed muscle and of fractions, was estimated during a basal period (2.5 h) and at 0.5-4 h intervals for 6 h of AA infusion. 3. Rates of mixed MPS were not significantly different from basal (0.076 +/- 0.008 % h(-1)) in the first 0.5 h of AA infusion but then rose rapidly to a peak after 2 h of approximately 2.8 times the basal value. Thereafter, rates declined rapidly to the basal value. All muscle fractions showed a similar pattern. 4. The results suggest that MPS responds rapidly to increased availability of AAs but is then inhibited, despite continued AA availability. These results suggest that the fed state accretion of muscle protein may be limited by a metabolic mechanism whenever the requirement for substrate for protein synthesis is exceeded.

Figure 1. Time course of serum insulin and glucose

*Values for insulin and glucose significantly above basal values.

Figure 2. Time course of rate of synthesis of mixed muscle proteins

*P < 0.05 vs. basal; †P < 0.05 vs. peak value.

Figure 3. Rates of synthesis of mixed muscle proteins and muscle fractions (myofibrillar, sarcoplasmic and mitochondrial proteins) during the basal period and during the infusion of the amino acid solution

The values shown are the averages over the time periods shown, estimated from biopsies taken at the beginnings and ends of the periods.