INFUSED IGF-I IGFBP-3 COMPLEX CAUSES GLOMERULAR LOCALIZATION OF IGF-IIN THE RAT-KIDNEY/

Insulin-like growth factor I(IGF-I) increases renal blood flow, glomer ular filtration rate (GFR), and proximal tubule reabsorption of phosph ate in humans and rodents. The biological effects of ICF-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 co uld be altered if given with selected IGF-binding proteins (IGFBPs). R ats were treated with intravenous injections of I-125-labeled IGF-I,I- 125-IGFBP-3, or I-125-IGFBP-4 alone or with complexes of I-125-IGF-I a nd IGFBP-3 or IGFBP-3. The cellular localization of IGF and the IGFBP within the kidney was then determined. I-125-IGF-I, I-125-IGFBP-4, and I-125-IGF-I/IGFBP-4 complexes were found almost exclusively in vacuol ar structures (endosomes) of proximal renal tubules. In contrast, abou t one-third of renal I-125-IGFBP-3 and I-125-IGF-I/IGFBP-3 was localiz ed to glomeruli. When I-125-IGF-I was given alone, 3% was found in glo meruli and 89% in proximal tubules. When given as I-125-IGF-I/IGFBP-3, 29% was in glomeruli and 65% in proximal tubules. We conclude that th e cellular localization of IGF-I within the kidney can be directed to glomerular elements if the IGF-I is given with IGFBP-3.