title: Use of a leucine clamp to demonstrate that IGF-I actively stimulates protein synthesis in normal humans.
abstract: Insulin-like growth factor I (IGF-I) is thought to mediate the anabolic action of growth hormone. A glucose and amino acid clamp technique was used to investigate the effects of a 3-h intravenous infusion of either 43.7 pmol.kg-1.min-1 (20 micrograms.kg-1.h-1) IGF-I or 3.4 pmol.kg-1.min-1 (0.5 mU.kg-1.min-1) insulin on whole body leucine turnover in five normal human volunteers. During the IGF-I infusion, IGF-I levels increased (P < 0.01; 26.6 +/- 2.8 to 88.9 +/- 14.2 nmol/l) and insulin levels fell (P < 0.05; 0.096 +/- 0.018 to 0.043 +/- 0.009 nmol/l). During the insulin infusion, insulin levels increased (P < 0.01; 0.057 +/- 0.013 to 0.340 +/- 0.099 nmol/l), and there was no change in IGF-I. There was no significant change in leucine production rate (Ra; a measure of protein degradation) during the IGF-I infusion (2.23 +/- 0.17 to 2.13 +/- 0.2 mumol.kg-1.min-1), but there was an increase (P < 0.03) in nonoxidative leucine disposal rate (Rd; a measure of protein synthesis; 1.83 +/- 0.15 to 2.05 +/- 0.21 mumol.kg-1.min-1). In contrast, insulin reduced (P < 0.02) leucine Ra (1.81 +/- 0.24 to 1.47 +/- 0.24 mumol.kg-1.min-1) and had no effect on nonoxidative leucine Rd (1.44 +/- 0.25 to 1.41 +/- 0.22 mumol.kg-1.min-1). We conclude that IGF-I, under conditions of adequate substrate supply, directly increases protein synthesis in contrast to insulin, which exerts its anabolic action by reducing proteolysis.
authors.affiliation: Department of Medicine, United Medical School, London, United Kingdom.
authors.forename: D L
authors.initials: DL
authors.lastname: Russell-Jones
authors.forename: A M
authors.initials: AM
authors.lastname: Umpleby
authors.forename: T R
authors.initials: TR
authors.lastname: Hennessy
authors.forename: S B
authors.initials: SB
authors.lastname: Bowes
authors.forename: F
authors.initials: F
authors.lastname: Shojaee-Moradie
authors.forename: K D
authors.initials: KD
authors.lastname: Hopkins
authors.forename: N C
authors.initials: NC
authors.lastname: Jackson
authors.forename: J M
authors.initials: JM
authors.lastname: Kelly
authors.forename: R H
authors.initials: RH
authors.lastname: Jones
authors.forename: P H
authors.initials: PH
authors.lastname: Sönksen
mesh_terms: D000328:Adult; D006801:Humans; D007328:Insulin / Q000097:blood / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology*; D007930:Leucine / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D014176:Protein Biosynthesis; D012016:Reference Values
chemical_list: D007328:Insulin; D007334:Insulin-Like Growth Factor I; D007930:Leucine