Inhibition of growth hormone action improves insulin sensitivity in liver IGF-1-deficient mice

Shoshana Yakar, Jennifer Setser, Hong Zhao, Bethel Stannard, Martin Haluzik, Vaida Glatt, Mary L. Bouxsein, John J. Kopchick, Derek LeRoith

Research output: Contribution to journalArticle


Liver IGF-1-deficient (LID) mice have a 75% reduction in circulating IGF-1 levels and, as a result, a fourfold increase in growth hormone (GH) secretion. To block GH action, LID mice were crossed with GH antagonist (GHa) transgenic mice. Inactivation of GH action in the resulting LID + GHa mice led to decreased blood glucose and insulin levels and improved peripheral insulin sensitivity. Hyperinsulinemic-euglycemic clamp studies showed that LID mice exhibit severe insulin resistance. In contrast, expression of the GH antagonist transgene in LID + GHa mice led to enhanced insulin sensitivity and increased insulin-stimulated glucose uptake in muscle and white adipose tissue. Interestingly, LID + GHa mice exhibit a twofold increase in white adipose tissue mass, as well as increased levels of serum-free fatty acids and triglycerides, but no increase in the triglyceride content of liver and muscle. In conclusion, these results show that despite low levels of circulating IGF-1, insulin sensitivity in LID mice could be improved by inactivating GH action, suggesting that chronic elevation of GH levels plays a major role in insulin resistance. These results suggest that IGF-1 plays a role in maintaining a fine balance between GH and insulin to promote normal carbohydrate and lipid metabolism.

Original languageEnglish (US)
Pages (from-to)96-105
Number of pages10
JournalJournal of Clinical Investigation
Issue number1
StatePublished - Jan 1 2004


ASJC Scopus subject areas

  • Medicine(all)

Cite this

Yakar, S., Setser, J., Zhao, H., Stannard, B., Haluzik, M., Glatt, V., Bouxsein, M. L., Kopchick, J. J., & LeRoith, D. (2004). Inhibition of growth hormone action improves insulin sensitivity in liver IGF-1-deficient mice. Journal of Clinical Investigation, 113(1), 96-105.