Preferential intestinal delivery of long[Arg3] insulin-like growth factor (LR3IGF-I) over IGF-I in preweaning and adult rats.
During early postnatal development, the intestine is highly responsive to LR(3)IGF-I administration but refractory to IGF-I, in contrast to the mature intestine. Given that LR(3)IGF-I is an IGF-I analog that binds poorly to IGF binding proteins, the response of the intestine is likely to reflect regulation of IGF-I bioactivity by IGF binding proteins. This study measures the delivery of exogenous IGF-I peptides to the intestine in preweaning (d-19) and adult rats to determine whether a correlation exists with the potency advantage of LR(3)IGF-I in the intestine during postnatal development. IGF-I or LR(3)IGF-I (2.6 microg/kg) was spiked with corresponding (125)I-labeled peptide (10 x 10(6) cpm) and administered iv as a bolus (n = 5-6/group) with blood and tissue samples collected 5 and 10 min post injection. In both age groups, the levels of (125)I-IGF-I retained in the blood at both 5 and 10 min were higher than the levels of (125)I-LR(3)IGF-I, consistent with the slower clearance rate for the native peptide. In the gastrointestinal tract, the levels of (125)I-LR(3)IGF-I per gram of tissue were 37-50% higher than (125)I-IGF-I. Surprisingly, there was little difference in the relative delivery of LR(3)IGF-I to IGF-I to the intestine, across developmental age. Although bolus iv-injected LR(3)IGF-I was cleared more rapidly from the circulation than IGF-I and was subsequently delivered to the intestine in higher amounts than the native peptide, the ratio of LR(3)IGF-I to IGF-I in gut tissues was approximately 2:1 in both age groups. Hence, selective delivery to the gut is unlikely to explain the markedly higher potency of (125)I-LR(3)IGF-I in stimulating growth of the preweaning vs. adult intestine.
Shoubridge
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Child Health Research Institute and Cooperative Research Centre for Tissue Growth and Repair, North Adelaide, South Australia 5006, Australia. cheryl.shoubridge@adelaide.edu.au
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D000375:Aging / Q000378:metabolism*; D000818:Animals; D000833:Animals, Suckling / Q000378:metabolism*; D001682:Biological Availability; D005260:Female; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics*; D007413:Intestinal Mucosa / Q000378:metabolism*; D010446:Peptide Fragments / Q000097:blood; D051381:Rats; D017208:Rats, Wistar
D018969:Insulin-Like Growth Factor Binding Proteins; C084339:LR(3)IGF-I; D010446:Peptide Fragments; D007334:Insulin-Like Growth Factor I