Insulin stimulates branched chain amino acid uptake and diminishes nitrogen flux from skeletal muscle of injured patients.
Resistance to insulin-mediated glucose disposal occurs in uninjured skeletal muscle of trauma patients but the effect of insulin on the accelerated proteolysis of trauma is unknown. We examined the influence of insulin on forearm amino acid and substrate exchange in five normals and four trauma patients using the hyperinsulinemic glucose clamp technique. Forearm substrate and amino acid flux (Q, nM/100 ml tissue/min), the product of blood flow and arterial deep venous concentration difference, was calculated before and during insulin infusion. Total nitrogen release (NQ, nM/100 ml tissue/min) was calculated as the algebraic sum of all nitrogen groups contained in the amino acids released. Among normal subjects, total nitrogen release from the forearm did not change (581 +/- 197 nM/100 ml tissue/min to 1167 +/- 455) during insulin infusion nor did total branched chain amino acid flux (0 +/- 30 nM/100 ml/min to 106 +/- 36). Under conditions of hyperinsulinemia, neither glutamine nor alanine changed in control subjects. In trauma patients, total nitrogen release (3843 +/- 1383 nM/100 ml/min) was inhibited during insulin administration (819 +/- 314, P less than 0.05). Total branched chain amino acid flux went from a net release of 460 +/- 134 nM/100 ml/min to a net uptake of 10 +/- 82 (P less than 0.05). In patients, statistically significant (P less than 0.05) differences were seen in individual amino acids as well. Forearm nitrogen flux was directly related to total branched chain amino acid flux in patients (r2 = 0.89). Additional studies in normals (n = 4) at higher insulin infusion rates confirmed that these effects were unique to injured subjects and not an effect of the insulin dose. Insulin attenuates the accelerated release of skeletal muscle amino acid in trauma patients. This effect may be mediated in part by facilitated branched chain amino acid uptake. The manipulation of both insulin and branched chain amino acid concentrations may provide a method to reduce post-traumatic protein catabolism.
D000328:Adult; D000597:Amino Acids, Branched-Chain / Q000378:metabolism*; D001481:Basal Metabolism; D005260:Female; D005542:Forearm / Q000098:blood supply / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000097:blood / Q000627:therapeutic use*; D007333:Insulin Resistance; D008297:Male; D009132:Muscles / Q000378:metabolism*; D009584:Nitrogen / Q000378:metabolism*; D014947:Wounds and Injuries / Q000188:drug therapy* / Q000378:metabolism
D000597:Amino Acids, Branched-Chain; D007328:Insulin; D005947:Glucose; D009584:Nitrogen