The effects of type 1 IGF receptor inhibition in a mouse model of diabetic kidney disease

Ariel Troib, Daniel Landau, Jack F. Youngren, Leonid Kachko, Ralph Rabkin, Yael Segev

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: We have recently shown increased sensitivity to IGF-I induced signal transduction in kidneys of diabetic mice. Accordingly we investigated the effects of PQ401, a novel diarylurea compound that inhibits IGF1R autophosphorylation in type I diabetes. Methods: Control (C) and Diabetic (D) mice were administered PQ401 (CP, DP) or vehicle (C, D) for 3. weeks. Results: CP animals showed a decrease in renal phosphorylated (p-)AKT and p-IGF1R. However, PQ401 had no effect on diabetic state (hyperglycemia, weight loss) or renal disease parameters (hypertrophy, hyperfiltration and albuminuria). Type IV collagen as well as TGF-β mRNA increased in DP and D compared to C. In the CP group renal hypertrophy with fat accumulation in proximal tubuli and increased renal IGF-I, collagen IV and TGF-β mRNA were seen. Conclusions: IGF1R inhibition by PQ401 exerted no significant effects on diabetic kidney disease parameters, arguing against a role for IGF-I in the pathogenesis of diabetic kidney disease. However, PQ401 affects normal kidneys, inducing renal hypertrophy as well as collagen and fat accumulation, with increased renal IGF-I mRNA, suggestive of a damage-regeneration process. Therefore, this diarylurea compound is not beneficial in early diabetic kidney disease. Its potential deleterious effects on kidney tissue need to be further investigated.

Original languageAmerican English
Pages (from-to)285-291
Number of pages7
JournalGrowth Hormone and IGF Research
Volume21
Issue number5
DOIs
StatePublished - 1 Oct 2011

Keywords

  • Diabetic nephropathy
  • Diarylurea
  • IGF-I
  • IGF1 receptor
  • Nephrotoxicity
  • Non-obese diabetic mice

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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