title: Interstitial fluid contains higher in vitro IGF bioactivity than serum: a study utilizing the suction blister technique.
abstract: BACKGROUND
  Circulating insulin-like growth factors (IGFs) are bound in complexes which affect their tissue-accessibility. Interstitial fluid is in close proximity to target cells, but the IGF-system is not well-described herein.
  
  
  OBJECTIVE
  To perform a thorough comparison of the IGF-system in suction blister fluid (SBF) vs. in serum, with emphasis on bioactive IGF levels.
  
  
  METHODS
  Eight hour study including samples collected in the fasting state (20 h) and after a meal.
  
  
  METHODS
  Clinical research facility.
  
  
  METHODS
  Six healthy males (age 37.0±8.8 years, BMI 22.5±1.4 kg/m(2)) (mean±SD).
  
  
  METHODS
  Serum and SBF concentrations of bioactive IGF (determined in vitro by specific IGF-I receptor (IGF-IR) phosphorylation assay), immunoreactive IGF and IGF binding protein (IGFBP) levels, Western ligand blotting (WLB) of IGFBPs and IGFBP-3 Western immunoblotting (WiB).
  
  
  RESULTS
  The ability of SBF to phosphorylate the IGF-IR in vitro was 41±27% higher than that of serum (P=0.007 by repeated measures ANOVA). By contrast, immunoreactive IGF and IGFBP-concentrations were approximately 50% lower in SBF than in serum (all P≤0.002). A marked difference in the composition of IGFBPs between serum and SBF was observed, including 3-fold elevated amounts of IGFBP-3 fragments in SBF (P<0.001). For both IGF-I, IGF-II and IGFBP-2, the effect of food intake differed between serum and SBF (all P≤0.03).
  
  
  CONCLUSIONS
  Despite lower concentrations, the in vitro IGF bioactivity was higher in SBF than in serum. This may relate to an increased enzymatic IGFBP-degradation and an altered IGFBP-composition in SBF, making more IGF-I and -II accessible to the IGF-IR. The impact of food intake on the IGF system differs between serum and interstitial fluid.
authors.affiliation: Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Denmark. uespelund@hotmail.com
authors.forename: Ulrick
authors.initials: U
authors.lastname: Espelund
authors.forename: Klaus
authors.initials: K
authors.lastname: Søndergaard
authors.forename: Peter
authors.initials: P
authors.lastname: Bjerring
authors.forename: Allan
authors.initials: A
authors.lastname: Flyvbjerg
authors.forename: Jan
authors.initials: J
authors.lastname: Frystyk
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D015153:Blotting, Western; D004435:Eating; D045604:Extracellular Fluid / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood / Q000378:metabolism; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D008297:Male; D013002:Somatomedins / Q000378:metabolism*
chemical_list: C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II