Compensatory alterations of insulin signal transduction in liver of growth hormone receptor knockout mice

Growth hormone (GH) deficiency is associated with increased sensitivity to insulin, but the molecular mechanisms involved in this association are poorly understood. In the current work, we have examined the consequences of the absence of the biological effects of GH on the first steps of the insulin...

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Veröffentlicht in:Journal of endocrinology 2000-09, Vol.166 (3), p.579-590
Hauptverfasser: Dominici, FP, Arostegui Diaz, G, Bartke, A, Kopchick, JJ, Turyn, D
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container_issue 3
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container_title Journal of endocrinology
container_volume 166
creator Dominici, FP
Arostegui Diaz, G
Bartke, A
Kopchick, JJ
Turyn, D
description Growth hormone (GH) deficiency is associated with increased sensitivity to insulin, but the molecular mechanisms involved in this association are poorly understood. In the current work, we have examined the consequences of the absence of the biological effects of GH on the first steps of the insulin signaling system in vivo in liver of mice with targeted disruption of the GH receptor/GH binding protein gene (GHR-KO mice). In these animals, circulating insulin concentrations are less than 4 microIU/ml, and glucose concentrations are low, concordant with a state of insulin hypersensitivity. The abundance and tyrosine phosphorylation state of the insulin receptor (IR), the IR substrate-1 (IRS-1), and Shc, the association between IRS-1 and the p85 subunit of phosphatidylinositol (PI) 3-kinase, the IRS-1- and the phosphotyrosine-associated PI 3-kinase in liver were examined. We found that, in liver of GHR-KO mice, the lack of GHR and GH eff! ects is associated with: (1) increased IR abundance, (2) increased insulin-stimulated IR tyrosine phosphorylation, (3) normal efficiency of IRS-1 and Shc tyrosine phosphorylation and (4) normal activation of PI 3-kinase by insulin. These alterations could represent an adaptation to the low insulin concentrations displayed by these animals, and may account for their increased insulin sensitivity.
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source MEDLINE; EZB-FREE-00999 freely available EZB journals
subjects Analysis of Variance
Animals
Biological and medical sciences
Endocrine pancreas
Female
Fundamental and applied biological sciences. Psychology
Glucose - metabolism
Hormones. Régulation
Immunoblotting - methods
Insulin - blood
Insulin - metabolism
Insulin Receptor Substrate Proteins
Liver - metabolism
Mice
Mice, Knockout
Phosphatidylinositol 3-Kinases - metabolism
Phosphoproteins - metabolism
Phosphorylation
Receptor, Insulin - metabolism
Receptors, Somatotropin - genetics
Signal Transduction
Tyrosine - metabolism
Vertebrates: endocrinology
title Compensatory alterations of insulin signal transduction in liver of growth hormone receptor knockout mice
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