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The effect of recombinant human IGF‐I on protein metabolism in post‐operative patients without nutrition compared to effects in experimental animals
Author(s) -
SANDSTRÖM R.,
SVANBERG E.,
HYLTANDER A.,
HAGLIND E.,
OHLSSON C.,
ZACHRISSON H.,
BERGLUND B.,
LINDHOLM E.,
BREVINGE H.,
LUNDHOLM K.
Publication year - 1995
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/j.1365-2362.1995.tb01958.x
Subject(s) - endocrinology , medicine , nitrogen balance , excretion , renal function , recombinant dna , chemistry , biochemistry , nitrogen , organic chemistry , gene
. 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 exo‐geneous substrate. Thirty patients who underwent elective colorectal surgery were randomized to receive either rhIGF‐I (80μg 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 ngmL ‐1 to a range of 300–450 ngmL ‐1 . In contrast, IGF‐I stimulated the synthesis of both globular and myofibrillar proteins (+50%, P <0.01), when given as a single dose (100μgkg ‐1 ) 2 h before measurements of protein synthesis in skeletal muscles of overnight fasted adult mice. This stimulatory effect by IGF‐I (1μgmL ‐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 postoperative patients is not clear, but was most likely explained by subnormal plasma concentrations of amino acids.