Studies involving the GH-IGF axis: Lessons from IGF-I and IGF-I receptor gene targeting mouse models

Shoshana Yakar, P. Pennisi, C. H. Kim, H. Zhao, Y. Toyoshima, O. Gavrilova, D. LeRoith

Research output: Contribution to journalArticle

Abstract

The IGFs are ubiquitous and have pleoitropic effects. They are critical for normal growth and development, and for normal functioning of adult tissues. A liver-specific gene-deletion knock-out of the IGF-I gene resulted in a mouse model with reduced circulating IGF-I levels, that led to insulin resistance due to the secondary elevation of circulating GH levels. The reduction in circulating IGF-I levels was also associated with a reduction in cancer growth and metastases in three cancer models, one for colon cancer and two for breast cancer. A second mouse model, using the transgenic approach, inhibited the IGF-I and insulin receptor function in skeletal muscle, and resulted in severe insulin resistance in muscle followed by insulin resistance in fat and liver and, eventually, β-cell dysfunction and development of Type 2 diabetes. This progression from insulin resistance to Type 2 diabetes was most likely due to lipotoxicity with elevated serum and tissue triglyceride levels. Evidence supporting the hypothesis came from the use of fibrates and leptin injections, each of which enhanced fatty acid (FA) oxidation in liver and muscle and was associated with a reversal of the insulin resistance and diabetes.

Original languageEnglish (US)
Pages (from-to)19-22
Number of pages4
JournalJournal of Endocrinological Investigation
Volume28
Issue number5 SUPPL
StatePublished - 2005

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IGF Type 1 Receptor
Gene Targeting
Insulin-Like Growth Factor I
Insulin Resistance
Type 2 Diabetes Mellitus
Liver
Breast Neoplasms
Fibric Acids
Muscles
Gene Knockout Techniques
Insulin Receptor
Gene Deletion
Leptin
Growth and Development
Colonic Neoplasms
Neoplasms
Skeletal Muscle
Triglycerides
Fatty Acids
Fats

Keywords

  • Gene-deletion mice models
  • IGF-I
  • IGF-I receptor
  • Transgenic mice

ASJC Scopus subject areas

  • Endocrinology

Cite this

Yakar, S., Pennisi, P., Kim, C. H., Zhao, H., Toyoshima, Y., Gavrilova, O., & LeRoith, D. (2005). Studies involving the GH-IGF axis: Lessons from IGF-I and IGF-I receptor gene targeting mouse models. Journal of Endocrinological Investigation, 28(5 SUPPL), 19-22.

Studies involving the GH-IGF axis : Lessons from IGF-I and IGF-I receptor gene targeting mouse models. / Yakar, Shoshana; Pennisi, P.; Kim, C. H.; Zhao, H.; Toyoshima, Y.; Gavrilova, O.; LeRoith, D.

In: Journal of Endocrinological Investigation, Vol. 28, No. 5 SUPPL, 2005, p. 19-22.

Research output: Contribution to journalArticle

Yakar, S, Pennisi, P, Kim, CH, Zhao, H, Toyoshima, Y, Gavrilova, O & LeRoith, D 2005, 'Studies involving the GH-IGF axis: Lessons from IGF-I and IGF-I receptor gene targeting mouse models', Journal of Endocrinological Investigation, vol. 28, no. 5 SUPPL, pp. 19-22.
Yakar, Shoshana ; Pennisi, P. ; Kim, C. H. ; Zhao, H. ; Toyoshima, Y. ; Gavrilova, O. ; LeRoith, D. / Studies involving the GH-IGF axis : Lessons from IGF-I and IGF-I receptor gene targeting mouse models. In: Journal of Endocrinological Investigation. 2005 ; Vol. 28, No. 5 SUPPL. pp. 19-22.
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