1 research outputs found
Kidney growth in normal and diabetic mice is not affected by human insulin-like growth factor binding protein-1 administration
Insulin-like growth factor I (IGF-I) accumulates in the kidney following
the onset of diabetes, initiating diabetic renal hypertrophy. Increased
renal IGF-I protein content, which is not reflected in messenger RNA
(mRNA) levels, suggests that renal IGF-I accumulation is due to
sequestration of circulating IGF-I rather than to local synthesis. It has
been suggested that IGF-I is trapped in the kidney by IGF binding protein
1 (IGFBP-1). We administered purified human IGFBP-1 (hIGFBP-1) to
nondiabetic and diabetic mice as three daily sc injections for 14 days,
starting 6 days after induction of streptozotocin diabetes when the
animals were overtly diabetic. Markers of early diabetic renal changes
(i.e., increased kidney weight, glomerular volume, and albuminuria)
coincided with accumulation of renal cortical IGF-I despite decreased mRNA
levels in 20-day diabetic mice. Human IGFBP-1 administration had no effect
on increased kidney weight or albuminuria in early diabetes, although it
abolished renal cortical IGF-I accumulation and glomerular hypertrophy in
diabetic mice. Increased IGF-I levels in kidneys of normal mice receiving
hIGFBP-1 were not reflected on kidney parameters. IGFBP-1 administration
in diabetic mice had only minor effects on diabetic renal changes.
Accordingly, these results did not support the hypothesis that IGFBP-1
plays a major role in early renal changes in diabetes