Growth hormone-induced insulin resistance

Role of the insulin receptor, IRS-1, GLUT-1 and GLUT-4

T. R. Smith, Jeffrey Elmendorf, T. S. David, J. Turinsky

Research output: Contribution to journalArticle

Abstract

Treatment of rats with growth hormone (GH; 1 mg/kg) s.c. twice daily over 2.5 days did not alter fasting plasma glucose or glucose tolerance, but increased fasting plasma insulin levels 64% and peak insulin response to a glucose load 35% over controls, indicating the development of insulin resistance. Studies on partially purified insulin receptors from soleus muscles showed that GH had no effect on insulin binding, but increased the abundance of insulin receptor β-subunits 27% as measured by immunoblotting. Despite this increase, GH abolished the increase in autophosphorylation of the insulin receptor β-subunit in response to physiological hyperinsulinemia, and diminished by 28% the response to supraphysiological hyperinsulinemia. Similarly, insulin- stimulated phosphorylation of IRS-1 was decreased 25% by GH but the abundance of IRS-1 was not affected. Studies on rats pretreated with streptozotocin suggested that the effects of GH are direct and not secondary to GH-induced hyperinsulinemia. Growth hormone decreased basal GLUT-1 abundance in the low-density microsome and plasma membrane fractions of epididymal adipocytes by 50 and 42%, respectively, but decreased basal GLUT-4 abundance only in the low-density microsome fraction by 24%. Despite these alterations, the abundance of both transporters in the plasma membrane fraction of adipocytes incubated with 0.1 U insulin/ml was not diminished by GH.

Original languageEnglish (US)
JournalFASEB Journal
Volume11
Issue number3
StatePublished - 1997
Externally publishedYes

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Insulin Receptor
insulin resistance
somatotropin
Growth Hormone
Insulin Resistance
insulin
hyperinsulinemia
Insulin
Hyperinsulinism
microsomes
Microsomes
adipocytes
Adipocytes
Glucose
fasting
Cell membranes
Fasting
plasma membrane
Cell Membrane
Rats

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Growth hormone-induced insulin resistance : Role of the insulin receptor, IRS-1, GLUT-1 and GLUT-4. / Smith, T. R.; Elmendorf, Jeffrey; David, T. S.; Turinsky, J.

In: FASEB Journal, Vol. 11, No. 3, 1997.

Research output: Contribution to journalArticle

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