EFFECT OF SHORT-TERM FASTING ON FREE DISSOCIABLE INSULIN-LIKE GROWTH-FACTOR-I CONCENTRATIONS IN NORMAL HUMAN SERUM/

A small portion of circulating insulin-like growth factor I (IGF-I) is detected in the free or readily dissociable state, which is thought t o be the metabolically active form. The amount of free/dissociable IGF -I in serum is dependent on a complex interplay between the production rate and the concentrations of IGF-I and IGF-binding proteins (IGFBPs ). IGF availability is also influenced by posttranslational changes in IGFBPs that affect the affinity of IGFBPs for IGF-I. In the present s tudy, we examined whether a short term fast (similar to 12 h) alters t he serum concentration of free/dissociable IGF-I, and whether these ch anges are associated with alterations in IGFBP-1 and the proteolysis s tatus of IGFBP-3. Circulating free/dissociable IGF-I concentrations, a s assessed by a two-site immunoradiometric assay, did not differ betwe en fasting and 4 h after a morning meal (1.48 +/- 0.07 vs. 1.50 +/- 0. 07 mu g/L, respectively). Likewise, free/dissociable IGF-I levels meas ured by RIA after separation by centrifugal ultrafiltration were not d ifferent between the two groups (1.43 +/- 0.14 vs. 1.38 +/- 0.18 mu g/ L, respectively). IGF-I bioactivity, as measured by thymidine incorpor ation by fibroblasts, did not differ in fasting and 4-h postprandial s era. There was no difference In IGFBP-3 and total acid-ethanol-extract able IGF-I concentrations in serum from fasted and fed subjects. In co ntrast, the concentration of IGFBP-1 in the serum was increased simila r to 5-fold in the fasted state compared to fed values. IGFBP-1 existe d in a highly phosphorylated form under fasting conditions. There was no change in IGFBP-3 proteolysis assessed either in vivo or in vitro b etween the fasting and fed states. The results indicate that a physiol ogically relevant short term overnight fast does not alter the circula ting levels of free/dissociable IGF-I despite a marked elevation in IG FBP-1.