Transgenic mice expressing human APP derived transgenes : M. Theisen 1), C. Czech 2), A. F. Macq 3), P. Delaère 4), U. Mönning 2), G. Tremp 4), L. Mercken 4), F. Perraud 1), D. Ali-Hadji 1), F. Mischler 1), K. Paliga 2), H. Baron, 4), J. B. Le Pecq 4), A. Pavirani 1), J. N. Octave 3) and K. Beyreuther

Abstract

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.To perform a thorough comparison of the IGF-system in suction blister fluid (SBF) vs. in serum, with emphasis on bioactive IGF levels.Eight hour study including samples collected in the fasting state (20 h) and after a meal.Clinical research facility.Six healthy males (age 37.0 ± 8.8 years, BMI 22.5 ± 1.4 kg/m2) (mean ± SD).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).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).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.