The growth hormone-insulin like growth factor axis revisited: Lessons from IGF-1 and IGF-1 receptor gene targeting

Shoshana Yakar, Hyunsook Kim, Hong Zhao, Yuka Toyoshima, Patricia Pennisi, Oksana Gavrilova, Derek LeRoith

Research output: Contribution to journalReview article

Abstract

We have created a liver-specific igf1 gene-deletion mouse model (LID) with markedly reduced circulating IGF-I levels. They demonstrate that while they have normal growth and development they develop insulin resistance secondary to the elevation of circulating growth hormone. When mated with an acid-labile subunit (ALS) gene-deleted mouse they also show osteopenia suggesting that circulating IGF-I levels play a significant role in bone formation. In a separate transgenic mouse we created a model of severe insulin resistance and type 2 diabetes by the overexpression of a dominant-negative IGF-I receptor in skeletal muscle. In this model we show that lipotoxicity plays a major role in the progression of the disease and is affected by treatment with a fibrate, which reverses the insulin resistance and diabetic state. These models are therefore very useful in studying human physiology and disease states.

Original languageEnglish (US)
Pages (from-to)251-254
Number of pages4
JournalPediatric Nephrology
Volume20
Issue number3 SPEC. ISS.
DOIs
StatePublished - Mar 1 2005

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Keywords

  • Insulin-like growth factor-1
  • Insulin-like growth factor-1 receptor
  • Lipotoxicity
  • Liver-specific igf1 deletion
  • Mouse model
  • Transgenic overexpression
  • Type2 diabetes

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Nephrology

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