DIFFERENTIAL REGULATION OF AMINO-ACID EXCHANGE AND PROTEIN DYNAMICS ACROSS SPLANCHNIC AND SKELETAL-MUSCLE BEDS BY INSULIN IN HEALTHY-HUMAN SUBJECTS

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 . kg(-1) . min(-1)) versus saline on protein dynamics across splanchnic and ske letal muscle (leg) beds were determined using stable isotopes of pheny lalanine, tyrosine, and leucine in 24 healthy subjects. After an overn ight fast, protein breakdown in muscle exceeded protein synthesis, cau sing a net release of amino acids from muscle bed, while in the splanc hnic bed protein synthesis exceeded protein breakdown, resulting 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 < 0.0 3) in the splanchnic region with no effect on protein breakdown, there by decreasing the net uptake of the amino acids. In addition, insulin also decreased (P < 0.001) leucine nitrogen flux substantially more th an leucine carbon flux, indicating increased leucine transamination (a n important biochemical process for nitrogen transfer between amino ac ids and across the organs), in a dose-dependent manner, with the magni tude 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 esse ntial proteins in the splanchnic bed. Insulin achieves amino acid bala nce across splanchnic and skeletal muscle beds through its differentia l effects on protein dynamics in these tissue beds.