Differential changes in free and total insulin-like growth factor I after major, elective abdominal surgery: the possible role of insulin-like growth factor-binding protein-3 proteolysis.
Major surgery is accompanied by extensive proteolysis of insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3). Proteolysis of IGFBP-3 is generally believed to increase IGF bioavailability due to a diminished affinity of the IGFBP-3 fragments for IGFs. We have investigated 18 patients undergoing elective ileo-anal J-pouch surgery. Patients were randomized to treatment with GH (12 IU/day; n = 9) or placebo (n = 9) from 2 days before to 7 days after operation. Free IGF-I and IGF-II were measured by ultrafiltration of serum, and IGFBP-3 proteolytic activity was determined by a [125I]recombinant human IGFBP-3 degradation assay. In the GH-treated group, total IGF-I increased preoperatively by 99%. Postoperatively, total IGF-I decreased by 48% (placebo) and 52% (GH). Immunoassayable IGFBP-3 decreased by 27% (placebo) and 26% (GH). In the placebo-treated group, free IGF-I was unchanged throughout the study. In the GH-treated group, free IGF-I increased by 277% preoperatively and remained elevated after operation. IGFBP-3 proteolytic activity increased by 63-73% after operation. The relative elevations of free IGF-I levels despite decreased total IGF-I levels could thus relate to augmented IGFBP-3 proteolysis.
Skjaerbaek
C
C
Medical Research Laboratories, Aarhus University, Denmark. cs@afdm.aau.dk
Frystyk
J
J
Orskov
H
H
Kissmeyer-Nielsen
P
P
Jensen
M B
MB
Laurberg
S
S
Møller
N
N
Flyvbjerg
A
A
D000328:Adult; D000704:Analysis of Variance; D003093:Colitis, Ulcerative / Q000601:surgery*; D004311:Double-Blind Method; D017558:Elective Surgical Procedures; D010450:Endopeptidases / Q000378:metabolism*; D005260:Female; D006801:Humans; D006868:Hydrolysis; D015592:Immunoradiometric Assay; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D016737:Proctocolectomy, Restorative
D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I; D010450:Endopeptidases