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

YAKAR, S; KIM, H; ZHAO, H; TOYOSHIMA Y; PENNISI, P; GAVRILOVA, O; LEROITH, D

PEDIATRIC NEPHROLOGY

Springer Berlin

Lugar: Berlin, Germany; Año: 2005 vol. Mar p. 251 - 254

0931-041X

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.