title: The effect of recombinant human IGF-I on protein metabolism in post-operative patients without nutrition compared to effects in experimental animals.
abstract: This study has evaluated the effects of recombinant human insulin-like growth factor I (rhIGF-I) to moderately stressed post-operative patients provided with dextrose as the only exogeneous substrate. Thirty patients who underwent elective colorectal surgery were randomized to receive either rhIGF-I (80 micrograms kg-1 bw) subcutaneously twice daily or placebo injections in a double-blind parallel group design. Nitrogen balance, urinary 3-methyl-histidine excretion plasma growth hormone (GH), serum cortisol, IGF-I binding proteins (IGFBP-1,3), glomerular filtration rate, plasma amino acid concentrations and whole-body energy expenditures were measured as effector variables during days 1-5 post-operatively. Animal and isolated tissue experiments were performed as additional control experiments to confirm cellular effectiveness of the recombinant material. rhIGF-I increased significantly the glomerular filtration rate and prevented the adaptive decrease in whole-body energy expenditure in response to partial starvation in the postoperative period. Serum and plasma concentrations of IGFBP-1,3 cortisol, blood glucose and amino acids were not significantly influenced by rhIGF-I administration, while plasma GH levels decreased significantly as expected. rhIGF-I had no effect on either nitrogen balance or protein breakdown (3-methylhistidine excretion) in post-operative patients on dextrose supplementation only, although plasma concentrations of IGF-I increased from 130-140 ng mL-1 to a range of 300-450 ng mL-1. In contrast, IGF-I stimulated the synthesis of both globular and myofibrillar proteins (+50%, P < 0.01), when given as a single dose (100 micrograms kg-1) 2 h before measurements of protein synthesis in skeletal muscles of overnight fasted adult mice. This stimulatory effect by IGF-I (1 microgram mL-1) was also confirmed by measurements of skeletal muscle protein synthesis in vitro (+40%, P < 0.05). Orally re-fed mice had a normal transcription of IGF-I mRNA in skeletal muscle cells, while overnight fasted mice showed a trend to down-regulated transcription. Our results demonstrate that rhIGF-I has several significant physiological effects, without major side-effects, when supplied to partially starved patients in the post-operative phase. The lack of a whole-body nitrogen sparing effect by rhIGF-I alone to post-operative patients is not clear, but was most likely explained by subnormal plasma concentrations of amino acids.
authors.affiliation: Department of Surgery, Sahlgrenska University Hospital, University of Göteborg, Sweden.
authors.forename: R
authors.initials: R
authors.lastname: Sandström
authors.forename: E
authors.initials: E
authors.lastname: Svanberg
authors.forename: A
authors.initials: A
authors.lastname: Hyltander
authors.forename: E
authors.initials: E
authors.lastname: Haglind
authors.forename: C
authors.initials: C
authors.lastname: Ohlsson
authors.forename: H
authors.initials: H
authors.lastname: Zachrisson
authors.forename: B
authors.initials: B
authors.lastname: Berglund
authors.forename: E
authors.initials: E
authors.lastname: Lindholm
authors.forename: H
authors.initials: H
authors.lastname: Brevinge
authors.forename: K
authors.initials: K
authors.lastname: Lundholm
mesh_terms: D000368:Aged; D000596:Amino Acids / Q000097:blood* / Q000187:drug effects*; D000818:Animals; D003107:Colorectal Surgery; D004311:Double-Blind Method; D005260:Female; D005508:Food Deprivation / Q000502:physiology*; D006801:Humans; D007279:Injections, Subcutaneous; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D011184:Postoperative Period; D011506:Proteins / Q000378:metabolism*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology
chemical_list: D000596:Amino Acids; D011506:Proteins; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I