title: Effects of recombinant human growth hormone on muscle protein turnover in malnourished hemodialysis patients.
abstract: To assess the effect of recombinant human growth hormone (rhGH) on muscle protein metabolism in uremic patients with malnutrition, forearm [3H]phenylalanine kinetics were evaluated in six chronically wasted (body weight 79% of ideal weight) hemodialysis (HD) patients in a self-controlled, crossover study. Forearm protein dynamics were evaluated before, after a 6-wk course of rhGH (5 mg thrice weekly) and after a 6-wk washout period. After rhGH: (a) forearm phenylalanine net balance--the difference between phenylalanine incorporation into and phenylalanine release from muscle proteins--decreased by 46% (-8+/-2 vs. -15+/-2 nmol/min x 100 ml at the baseline and -11+/-2 after washout, P < 0.02); (b) phenylalanine rate of disposal, an index of protein synthesis, increased by 25% (25+/-5 vs. 20+/-5 at the baseline and 20+/-4 after washout, P < 0.03); (c) phenylalanine rate of appearance, an index of protein degradation, was unchanged (33+/-5 vs. 35+/-5 at the baseline and 31+/-4 after washout); (d) forearm potassium release declined (0.24+/-0.13 vs. 0.60+/-0.15 microeq/min at the baseline, and 0.42+/-0.20 microeq/min after washout P < 0.03); (e) changes in the insulin-like growth factor binding protein (IGFBP)-1 levels and insulin-like growth factor-I (IGF-I)/IGFBP-3 ratios accounted for 15.1% and 47.1% of the percent variations in forearm net phenylalanine balance, respectively. Together, these two factors accounted for 62.2% of variations in forearm net phenylalanine balance during and after rhGH administration. These data indicate: (a) that rhGH administration in malnourished hemodialysis patients is followed by an increase in muscle protein synthesis and by a decrease in the negative muscle protein balance observed in the postabsorptive state; and (b) that the reduction in net protein catabolism obtained with rhGH can be accounted for by the associated changes in circulating free, but not total, IGF-I levels.
authors.affiliation: Department of Internal Medicine, University of Genoa, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Garibotto
authors.forename: A
authors.initials: A
authors.lastname: Barreca
authors.forename: R
authors.initials: R
authors.lastname: Russo
authors.forename: A
authors.initials: A
authors.lastname: Sofia
authors.forename: P
authors.initials: P
authors.lastname: Araghi
authors.forename: A
authors.initials: A
authors.lastname: Cesarone
authors.forename: M
authors.initials: M
authors.lastname: Malaspina
authors.forename: F
authors.initials: F
authors.lastname: Fiorini
authors.forename: F
authors.initials: F
authors.lastname: Minuto
authors.forename: A
authors.initials: A
authors.lastname: Tizianello
mesh_terms: D000328:Adult; D000368:Aged; D000596:Amino Acids / Q000378:metabolism; D005260:Female; D019382:Human Growth Hormone / Q000494:pharmacology*; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000378:metabolism; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000378:metabolism / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D009748:Nutrition Disorders / Q000150:complications / Q000378:metabolism*; D010649:Phenylalanine / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology*; D012044:Regression Analysis; D006435:Renal Dialysis / Q000009:adverse effects
chemical_list: D000596:Amino Acids; D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D018972:Insulin-Like Growth Factor Binding Protein 3; D009124:Muscle Proteins; D011994:Recombinant Proteins; D019382:Human Growth Hormone; D010649:Phenylalanine; D007334:Insulin-Like Growth Factor I; D011188:Potassium; D006854:Hydrocortisone