STIMULATION OF PROTEIN-SYNTHESIS IN PIG SKELETAL-MUSCLE BY INFUSION OF AMINO-ACIDS DURING CONSTANT INSULIN AVAILABILITY

Incorporation Of L-[J-C-13]leucine into muscle protein and leg exchange of L-[N-15]phenylalanine were used to assess the effects over 240 min of amino acid supply on leg protein turnover in anesthetized, overnight-fasted (Landrace x Great White) female pigs. In all pigs, plasma insulin and glucagon stability was ensured by infusion of somatostatin (8 mug.kg-1.h-1), insulin (6 mU.kg-1.h-1), and glucagon (72 ng.kg-1.h-1). Mixed amino acid infusion (260 mg.kg-1.h-1) caused a 2- to 2.5-fold elevation of arterial plasma phenylalanine and leucine; in a control group (no amino acid infusion), an increase in phenylalanine and leucine concentration was observed as a result of the hormone clamp. Plasma insulin and glucagon concentrations were steady and not significantly different between control and amino acid-infused groups during the final 240 min, but plasma glucose fell (P < 0.05) in both groups (4.57 +/- 0.17 to 3.15 +/-0.73 mM). Muscle protein synthetic rate (estimated from the change in L-[1-C-13]leucine incorporation compared with labeling of [C-13]leucyl-tRNA) was greater in amino acid-infused (0. 076%/h) than in control (0.053%/h) pigs. In the control group, leg amino acid balance was negative (Phe alone, -10.2 +/- 9.4 nmol Phe.100 g-1.min-1; total amino acids, -0.27 +/- 1.04 mug amino N.100 g-1.min-1), but during amino acid infusion, balance was positive (Phe alone, +33.6 +/- 8.8 nmol Phe.100 g-1.min-1; total amino acids, +58.2 +/- 4.9 mug amino N.100 g-1.min-1). Leg phenylalanine release (i.e., leg muscle protein breakdown) was greater in the amino acid-infused group (140.9 +/- 14.9 nmol.100 g-1.min-1) than in the controls (57.1 +/- 9.3 nmol.100 g-1.min-1), but because of a greater coincident phenylalanine balance, phenylalanine uptake into leg muscle (i.e., apparent leg muscle protein synthesis) appeared to be greater during amino acid infusion (172.6 +/- 19.1 vs. 46.9 +/- 8.4 nmol.100 g-1.min-1 ;P < 0.005). The effects on leucine carbon (leucine + alpha-ketoisocaproate) leg balance, appearance, and disposal were consistent with the results for phenylalanine. The results confirm a stimulatory effect of amino acids alone on skeletal muscle protein synthesis and suggest that the mechanisms involved may include increased sensitivity of protein synthesis to insulin at high amino acid concentrations, but not alterations in the secretion of pancreatic hormones.