Infused IGF-I/IGFBP-3 complex causes glomerular localization of IGF-I in the rat kidney.
Insulin-like growth factor I (IGF-I) increases renal blood flow, glomerular filtration rate (GFR), and proximal tubule reabsorption of phosphate in humans and rodents. The biological effects of IGF-I are likely to be influenced by cellular localization of IGF-I within the kidney. We therefore tested whether the renal localization of infused IGF-I could be altered if given with selected IGF-binding proteins (IGFBPs). Rats were treated with intravenous injections of 125I-labeled IGF-I, 125I-IGFBP-3, or 125I-IGFBP-4 alone or with complexes of 125I-IGF-I and IGFBP-3 or IGFBP-4. The cellular localization of IGF and the IGFBP within the kidney was then determined. 125I-IGF-I, 125I-IGFBP-4, and 125I-IGF-I/IGFBP-4 complexes were found almost exclusively in vacuolar structures (endosomes) of proximal renal tubules. In contrast, about one-third of renal 125I-IGFBP-3 and 125I-IGF-I/IGFBP-3 was localized to glomeruli. When 125I-IGF-I was given alone, 3% was found in glomeruli and 89% in proximal tubules. When given as 125I-IGF-I/IGFBP-3, 29% was in glomeruli and 65% in proximal tubules. We conclude that the cellular localization of IGF-I within the kidney can be directed to glomerular elements if the IGF-I is given with IGFBP-3.
Department of Internal Medicine, Diabetes and Endocrinology Research Center, Veterans Administration Medical Center, The University of Iowa, Iowa City, Iowa 52246, USA.
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Stokes
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D000818:Animals; D001345:Autoradiography; D003432:Cross-Linking Reagents; D006801:Humans; D007262:Infusions, Intravenous; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000008:administration & dosage / Q000493:pharmacokinetics*; D018974:Insulin-Like Growth Factor Binding Protein 4 / Q000493:pharmacokinetics; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D007678:Kidney Glomerulus / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D007685:Kidney Tubules, Collecting / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D007686:Kidney Tubules, Distal / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D003432:Cross-Linking Reagents; D018972:Insulin-Like Growth Factor Binding Protein 3; D018974:Insulin-Like Growth Factor Binding Protein 4; D007457:Iodine Radioisotopes; D007334:Insulin-Like Growth Factor I