Objective: Increase in kidney IGF-I levels due to its increased trapping from the circulation was hypothesized to be a key mediator of compensatory renal enlargement. We tested this hypothesis using genetically engineered mice with extremely low circulating IGF-I levels. Design: Both IGF-I deficient (ID) and normal (N) mice underwent a uninephrectomy (UNx) and sacrificed 2 or 9. days later. Results: Initial body weight (BW) and kidney weight (KW) were significantly reduced in ID vs. N mice, while KW/BW ratios were similar. KW increased post-UNx to a comparable extent in ID and N mice (125 ± 4 and 118 ± 6% of pre-UNx KW, p < 0.05 vs. C). Kidney IGF-I mRNA levels were similar in the ID and N mice and did not change post-UNx. Kidney IGF-I peptide levels pre-UNx were significantly lower in ID vs. N mice (25 ± 5 vs. 305 ± 39. ng/g) and increased in both groups after UNx, remaining low in ID mice (45 ± 4 in ID vs 561 ± 64. ng/g in N). IGF type 1 receptor phosphorylation was unchanged. Conclusion: While a severe deficiency of circulating IGF-I impairs body growth, UNx induces a significant and proportional increase in renal mass in ID mice despite markedly decreased kidney IGF-I levels (> 90% reduction) and no significant change in receptor phosphorylation. This all suggests that factors other than circulating and locally produced IGF-I are responsible for compensatory renal enlargement.
- Gene disruption
- Insulin-like growth factor I
- Renal hypertrophy
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism