title: Ascites from patients with alcoholic liver cirrhosis contains higher IGF-I bioactivity than serum.
abstract: OBJECTIVE
  Patients with liver cirrhosis have diminished hepatic IGF-I generation, resulting in low circulating levels, whereas data on IGF-I in ascites are sparse. Therefore, we compared the IGF-system in serum and ascites from cirrhotic patients.
  
  
  METHODS
  The study comprised 43 patients (12 females) with ascites and liver function of 58 +/- 10% of normal. Serum and ascites were collected concomitantly in the fasting state. In 11 patients, second serum and ascitic samples were collected within the first week. Eleven matched controls were also included. All samples were assayed for IGF-related parameters by immunoassays and by cell-based IGF-I bioassay.
  
  
  RESULTS
  As compared with controls, serum total IGF-I, total IGF-II, pro-IGF-II and bioactive IGF-I were reduced in liver patients, whereas IGF-binding protein 1 (IGFBP-1), IGFBP-2 and the soluble IGF-II receptor were elevated (P < 0.005 for all). In ascites, all IGF-related peptides but pro-IGF-II were further reduced as compared with serum (P < 0.001). By contrast, bioactive IGF-I was fourfold elevated in ascites as compared with serum (2.20 +/- 0.33 vs. 0.55 +/- 0.08 microg/l, P < 0.001). In ascites, the IGF-I bioactivity signal was completely blocked by addition of IGFBP-3. Repetitive measurements (n = 11) in ascites showed that all peptides but IGFBP-1 remained unchanged within 1 week.
  
  
  CONCLUSIONS
  It is a novel observation that the in vitro bioactivity of IGF-I can be higher in fluids from an extravascular compartment than in serum, in contrast to immunoreactive levels. This supports different roles for endocrine and paracrine/autocrine IGF-I, but the pathophysiological significance of our observation remains to be clarified.
authors.affiliation: The Medical Research Laboratories, Clinical Institute, and Medical Department M (Diabetes & Endocrinology), Aarhus University Hospital, DK-8000 Aarhus C, Denmark.
authors.forename: Nilani
authors.initials: N
authors.lastname: Jeyaratnaganthan
authors.forename: Henning
authors.initials: H
authors.lastname: Grønbaek
authors.forename: Peter
authors.initials: P
authors.lastname: Holland-Fischer
authors.forename: Ulrick
authors.initials: U
authors.lastname: Espelund
authors.forename: Jian-Wen
authors.initials: JW
authors.lastname: Chen
authors.forename: Allan
authors.initials: A
authors.lastname: Flyvbjerg
authors.forename: Hendrik
authors.initials: H
authors.lastname: Vilstrup
authors.forename: Jan
authors.initials: J
authors.lastname: Frystyk
mesh_terms: D001201:Ascites / Q000097:blood / Q000150:complications / Q000378:metabolism*; D005260:Female; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood / Q000378:metabolism; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000097:blood / Q000378:metabolism; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D016014:Linear Models; D008104:Liver Cirrhosis, Alcoholic / Q000097:blood / Q000150:complications / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis
chemical_list: D018970:Insulin-Like Growth Factor Binding Protein 1; D018971:Insulin-Like Growth Factor Binding Protein 2; D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II