Insulin selectively attenuates breakdown of nonmyofibrillar proteins in peripheral tissues of normal men.

The role of insulin to control protein synthesis and degradation in the human leg and forearm was investigated in eight healthy individuals. The glucose clamp technique with simultaneous infusion of crystalline amino acids were used to create hyperinsulinemia (100-120 mU/l) in combination with euglycemia and elevated plasma concentrations of amino acids (> 4 mmol/l). A primed constant infusion with L-[U-14C]tyrosine and L-[phenyl-2H5]phenylalanine was used for simultaneous measurements of the disposal (protein synthesis) and the release (protein degradation) of tyrosine and phenylalanine, respectively, across the leg and forearm before and during hyperinsulinemia. The balance of 3-methylhistidine was also determined as a measure of muscle breakdown. Insulin stimulated tissue glucose and net amino acid uptake across the arm and leg tissues, whereas the disposal of both tyrosine and phenylalanine (protein synthesis) was not stimulated across the arm and the leg during hyperinsulinemia. The release of tyrosine and phenylalanine was significantly decreased from both leg and arm tissues (protein degradation) in response to insulin. However, the release of 3-methylhistidine from skeletal muscles was totally unaffected by hyperinsulinemia. We conclude that it is unlikely that insulin contributes to the normal stimulation of protein synthesis during feeding in humans and that insulin has no effect on breakdown of the large myofibrillar protein pool in skeletal muscles in unstressed individuals.