Growth hormone-induced insulin resistance: Role of the insulin receptor, IRS-1, GLUT-1, and GLUT-4

Terry R. Smith, Jeffrey Elmendorf, Tonya S. David, Jiri Turinsky

Research output: Contribution to journalArticle

87 Citations (Scopus)

Abstract

Treatment of rats with growth hormone (GH; 1 mg/kg sc) twice daily over 2.5 days did not alter fasting plasma glucose or glucose tolerance but increased fasting plasma insulin levels 65% and peak insulin response to a glucose lead 35% over controls, indicating the development of insulin resistance. Studies on partially purified insulin receptors from soleus muscles showed that GH increased the abundance of insulin receptor β- subunits by 48% 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 insulin receptor substrate-1 (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. GH 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)
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume272
Issue number6 35-6
StatePublished - Jun 1997
Externally publishedYes

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Insulin Receptor Substrate Proteins
Insulin Receptor
Growth Hormone
Insulin Resistance
Hyperinsulinism
Insulin
Microsomes
Adipocytes
Glucose
Fasting
Cell membranes
Cell Membrane
Rats
Plasmas
Streptozocin
Immunoblotting
Phosphorylation
Skeletal Muscle
Muscle

Keywords

  • Glucose transporters
  • Hormone interaction
  • Signal transduction

ASJC Scopus subject areas

  • Physiology
  • Endocrinology
  • Biochemistry
  • Physiology (medical)

Cite this

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

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 272, No. 6 35-6, 06.1997.

Research output: Contribution to journalArticle

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