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Updated: Jul 30, 2026

Studying the Hypothalamic Insulin Signal to Peripheral Glucose Intolerance with a Continuous Drug Infusion System into the Mouse Brain
Published on: January 4, 2018
The growth hormone-insulin like growth factor axis revisited: lessons from IGF-1 and IGF-1 receptor gene targeting
Shoshana Yakar1, Hyunsook Kim, Hong Zhao
1Diabetes Branch, National Institutes of Health, MSC 1758, Bethesda, MD 20892-1758, USA.
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.
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