9227454

pubmed:Citation

6 Pt 1

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 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 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.

eng

IM

MEDLINE

0002-9513

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NLM

E1071-9

pubmed-meshheading:9227454-Adipocytes, pubmed-meshheading:9227454-Animals, pubmed-meshheading:9227454-Blood Glucose, pubmed-meshheading:9227454-Diabetes Mellitus, Experimental, pubmed-meshheading:9227454-Glucose Tolerance Test, pubmed-meshheading:9227454-Glucose Transporter Type 1, pubmed-meshheading:9227454-Glucose Transporter Type 4, pubmed-meshheading:9227454-Growth Hormone, pubmed-meshheading:9227454-Insulin, pubmed-meshheading:9227454-Insulin Receptor Substrate Proteins, pubmed-meshheading:9227454-Insulin Resistance, pubmed-meshheading:9227454-Male, pubmed-meshheading:9227454-Monosaccharide Transport Proteins, pubmed-meshheading:9227454-Muscle, Skeletal, pubmed-meshheading:9227454-Muscle Proteins, pubmed-meshheading:9227454-Phosphoproteins, pubmed-meshheading:9227454-Phosphorylation, pubmed-meshheading:9227454-Rats, pubmed-meshheading:9227454-Rats, Sprague-Dawley, pubmed-meshheading:9227454-Receptor, Insulin, pubmed-meshheading:9227454-Time Factors

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

Journal Article, Research Support, U.S. Gov't, P.H.S.