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

Abstract

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
Volume113
Issue number1
DOIs
StatePublished - Jan 2004

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Insulin-Like Growth Factor I
Growth Hormone
Insulin Resistance
Liver
Hormone Antagonists
White Adipose Tissue
Insulin
Triglycerides
Muscles
Glucose Clamp Technique
Carbohydrate Metabolism
Transgenes
Lipid Metabolism
Nonesterified Fatty Acids
Transgenic Mice
Blood Glucose
Glucose
Serum

ASJC Scopus subject areas

  • Medicine(all)

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Inhibition of growth hormone action improves insulin sensitivity in liver IGF-1-deficient mice. / Yakar, Shoshana; Setser, Jennifer; Zhao, Hong; Stannard, Bethel; Haluzik, Martin; Glatt, Vaida; Bouxsein, Mary L.; Kopchick, John J.; LeRoith, Derek.

In: Journal of Clinical Investigation, Vol. 113, No. 1, 01.2004, p. 96-105.

Research output: Contribution to journalArticle

Yakar, S, Setser, J, Zhao, H, Stannard, B, Haluzik, M, Glatt, V, Bouxsein, ML, Kopchick, JJ & LeRoith, D 2004, 'Inhibition of growth hormone action improves insulin sensitivity in liver IGF-1-deficient mice', Journal of Clinical Investigation, vol. 113, no. 1, pp. 96-105. https://doi.org/10.1172/JCI200417763
Yakar, Shoshana ; Setser, Jennifer ; Zhao, Hong ; Stannard, Bethel ; Haluzik, Martin ; Glatt, Vaida ; Bouxsein, Mary L. ; Kopchick, John J. ; LeRoith, Derek. / Inhibition of growth hormone action improves insulin sensitivity in liver IGF-1-deficient mice. In: Journal of Clinical Investigation. 2004 ; Vol. 113, No. 1. pp. 96-105.
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