A marked deficiency in circulating and renal IGF-I peptide does not inhibit compensatory renal enlargement in uninephrectomized mice

Daniel Landau, Jaclyn Biada, Yu Chen, Sumita Sood, Shoshana Yakar, Derek LeRoith, Yael Segev, Ralph Rabkin

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)279-284
Number of pages6
JournalGrowth Hormone and IGF Research
Volume21
Issue number5
DOIs
StatePublished - Oct 2011

Fingerprint

Insulin-Like Growth Factor I
Kidney
Peptides
Weights and Measures
Body Weight
Phosphorylation

Keywords

  • Animal
  • Gene disruption
  • Insulin-like growth factor I
  • Knockout
  • Mice
  • Models
  • Renal hypertrophy
  • Uninephrectomy

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

A marked deficiency in circulating and renal IGF-I peptide does not inhibit compensatory renal enlargement in uninephrectomized mice. / Landau, Daniel; Biada, Jaclyn; Chen, Yu; Sood, Sumita; Yakar, Shoshana; LeRoith, Derek; Segev, Yael; Rabkin, Ralph.

In: Growth Hormone and IGF Research, Vol. 21, No. 5, 10.2011, p. 279-284.

Research output: Contribution to journalArticle

Landau, Daniel ; Biada, Jaclyn ; Chen, Yu ; Sood, Sumita ; Yakar, Shoshana ; LeRoith, Derek ; Segev, Yael ; Rabkin, Ralph. / A marked deficiency in circulating and renal IGF-I peptide does not inhibit compensatory renal enlargement in uninephrectomized mice. In: Growth Hormone and IGF Research. 2011 ; Vol. 21, No. 5. pp. 279-284.
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abstract = "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.",
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AU - LeRoith, Derek

AU - Segev, Yael

AU - Rabkin, Ralph

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