TRANSFER OF INSULIN-LIKE GROWTH-FACTOR (IGF)-I FROM BLOOD TO INTESTINE - COMPARISON WITH IGFS THAT BIND POORLY TO IGF-BINDING PROTEINS

The net transfer of I-125-labelled insulin-like growth factor (IGF)-I from the blood to the distal small intestine was measured in anaesthet ized lambs using a non-recirculating vascular-perfused intestine. To d etermine whether IGF-binding proteins (IGFBPs) reduce net IGF transfer , radiolabelled IGF-I was compared with two analogues, des(1-3)IGF-I a nd LR(3)IGF-I, which show reduced affinity for IGFBPs. Radiolabelled I GF-I, des(1-3)IGF-I or LR(3)IGF-I (1 ng/ml plasma) was infused for 45 min into the arterial supply of a 10 cm intestinal segment, either in the absence of added unlabelled peptide (high specific activity) or in the presence of a 100-fold excess of unlabelled homologous peptide (l ow specific activity) to achieve different proportions of h-ee and com plexed peptide. Very Little degradation of radiolabelled peptides was detected in plasma, with 3-10% degradation in the intestinal tissue. L ess than 5% of radiolabelled IGF-I remained as free peptide in the eff erent venous plasma of the perfused segment at both specific activitie s. Bound radiolabelled IGF-I was found by size-exclusion chromatograph y mainly in the 30-50 kDa region, with a smaller proportion in the 150 kDa peak. The net intestinal transfer of IGF-I, calculated as the sum of the proportions of infused tracer recovered from intestinal tissue , luminal contents and lymph, was 3.46 +/- 0.22% (S.E.M.) and 3.49 +/- 0.93% when infused at high and low specific activities respectively. The analogues differed from IGF-I with up to ninefold higher concentra tions of free radiolabelled peptide in venous plasma of the perfused i ntestinal segment, and corresponding decreases in binding to the 30-50 kDa binding proteins. Notwithstanding these marked differences in the plasma levels of free peptide, net intestinal transfer was very simil ar for the three peptides, as was the extent of degradation in the int estinal tissue. The lack of correlation between binding to 30-50 kDa b inding proteins and net intestinal transfer suggests that association with 30-50 kDa plasma binding proteins is not a rate-limiting determin ant of net IGF transfer to intestinal tissue.