title: Insulin infusion increases levels of free IGF-I and IGFBP-3 proteolytic activity in patients after surgery.
abstract: We have studied the effects of insulin on the bioavailability of insulin-like growth factor (IGF) I in insulin-resistant patients after surgery. Serum levels of total IGF-I (tIGF-I), free IGF (fIGF)-I, fIGF-II, and IGF-binding protein (IGFBP) 1 and IGFBP-3 proteolytic activity (IGFBP-3-PA), determined on the day before surgery and on the 1st postoperative day, were related to insulin sensitivity measured by a hyperinsulinemic, normoglycemic clamp. Before surgery, the decreased tIGF-I (P < 0.05) in response to insulin infusion was accompanied by an 18% reduction of IGFBP-1 (P < 0.001), while IGFBP-3-PA remained unchanged. Levels of fIGF-I and fIGF-II were not changed by insulin infusions. After surgery, IGFBP-3-PA increased (P < 0.05) during insulin infusion, and this was associated with an increase in tIGF-I (P < 0.001) and fIGF-I (P < 0.01), while no significant change was found in fIGF-II. The reduction in IGFBP-1 in response to insulin infusion was not affected by surgery. The change in IGFBP-3-PA during insulin infusion after surgery was related to the corresponding change in fIGF-I (r(2) = 0.26, P < 0.05) and postoperative insulin sensitivity (r(2) = -0.22, P < 0.05). These data suggest that increased IGFBP-3-PA during insulin infusion after surgery governs the increased levels of fIGF-I, while insulin-induced suppression of IGFBP-1 was not affected by surgery. We propose that, in catabolic, postoperative patients, increased levels of insulin from exogenous or, possibly, endogenous sources (nutritionally induced) may be a signal to increase IGF-I bioavailability by increased expression of IGFBP-3-PA to counteract further deterioration in glucose metabolism.
authors.affiliation: Center of Gastrointestinal Disease, Ersta Hospital and Karolinska Institute, Karolinska Hospital, Stockholm, Sweden. jonas.nygren@ersta.se
authors.forename: J
authors.initials: J
authors.lastname: Nygren
authors.forename: C
authors.initials: C
authors.lastname: Carlsson-Skwirut
authors.forename: K
authors.initials: K
authors.lastname: Brismar
authors.forename: A
authors.initials: A
authors.lastname: Thorell
authors.forename: O
authors.initials: O
authors.lastname: Ljungqvist
authors.forename: P
authors.initials: P
authors.lastname: Bang
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000601:surgery; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D006946:Hyperinsulinism; D015592:Immunoradiometric Assay; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000097:blood* / Q000494:pharmacology*; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D007410:Intestinal Diseases / Q000601:surgery; D007680:Kidney Neoplasms / Q000601:surgery; D008297:Male; D008875:Middle Aged; D011184:Postoperative Period; D012044:Regression Analysis; D014462:Ultrafiltration
chemical_list: D001786:Blood Glucose; D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II