Vol. 275, Issue 1, E32-E37, July 1998
Infused IGF-I/IGFBP-3 complex causes glomerular localization
of IGF-I in the rat kidney
Alexander
Sandra,
Mary
Boes,
Brian L.
Dake,
John B.
Stokes, and
Robert S.
Bar
Departments of Internal Medicine and Anatomy, Diabetes and
Endocrinology Research Center, Veterans Administration Medical Center,
The University of Iowa, Iowa City, Iowa 52246
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.
renal redistribution of insulin-like growth factors
