Growth hormone-induced insulin resistance: role of the insulin
receptor, irs-1, glut-1 and glut-4.
Smith, Terry R., Jeffrey S. Elmendorf, Tonya S. David, and Jiri
Turinsky.
Department of Physiology and Cell Biology, Albany Medical College,
Albany, NY 12208
APStracts 4:0034E, 1997.
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 increased the
abundance of insulin receptor [beta]-subunits by 48% as measured by
immunoblotting. Despite this increase, GH abolished the increase in
autophosphorylation of the insulin receptor [beta]-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.
Received 18 July 1996; accepted in final form 9 January 1997.
APS Manuscript Number E343-6.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 19 February 1997