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Autocrine IGF-1 Action in Adipocytes Controls Systemic IGF-1 Concentrations and Growth
by
Nora Klöting
, Jens C. Brüning
, Thomas Wunderlich
, Matthias Kern
, Linda Koch
, Wilhelm Krone
, Matthias Blüher
, Karen Ruschke
in
Adipocytes
/ Adipocytes - cytology
/ Adipocytes - metabolism
/ Adipose Tissue - cytology
/ Adipose Tissue - metabolism
/ Animals
/ Biological and medical sciences
/ Body fat
/ Body Weight - physiology
/ Cells, Cultured
/ Company growth
/ Diabetes. Impaired glucose tolerance
/ Eating - physiology
/ Endocrine pancreas. Apud cells (diseases)
/ Endocrinopathies
/ Etiopathogenesis. Screening. Investigations. Target tissue resistance
/ Fat cells
/ Gene Deletion
/ Gene Expression
/ Glucose - metabolism
/ Growth
/ Insulin
/ Insulin-like growth factor 1
/ Insulin-Like Growth Factor Binding Protein 3 - blood
/ Insulin-like growth factor I
/ Insulin-Like Growth Factor I - genetics
/ Insulin-Like Growth Factor I - metabolism
/ Insulin-Like Growth Factor I - physiology
/ Kinases
/ Medical sciences
/ Mice
/ Mice, Inbred C57BL
/ Mice, Knockout
/ Musculoskeletal system
/ Phenotype
/ Physiological aspects
/ Receptor, IGF Type 1 - genetics
/ Receptor, IGF Type 1 - physiology
/ Research design
/ Reverse Transcriptase Polymerase Chain Reaction
/ RNA, Messenger - genetics
/ RNA, Messenger - metabolism
/ Signal Transduction
2008
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Autocrine IGF-1 Action in Adipocytes Controls Systemic IGF-1 Concentrations and Growth
by
Nora Klöting
, Jens C. Brüning
, Thomas Wunderlich
, Matthias Kern
, Linda Koch
, Wilhelm Krone
, Matthias Blüher
, Karen Ruschke
in
Adipocytes
/ Adipocytes - cytology
/ Adipocytes - metabolism
/ Adipose Tissue - cytology
/ Adipose Tissue - metabolism
/ Animals
/ Biological and medical sciences
/ Body fat
/ Body Weight - physiology
/ Cells, Cultured
/ Company growth
/ Diabetes. Impaired glucose tolerance
/ Eating - physiology
/ Endocrine pancreas. Apud cells (diseases)
/ Endocrinopathies
/ Etiopathogenesis. Screening. Investigations. Target tissue resistance
/ Fat cells
/ Gene Deletion
/ Gene Expression
/ Glucose - metabolism
/ Growth
/ Insulin
/ Insulin-like growth factor 1
/ Insulin-Like Growth Factor Binding Protein 3 - blood
/ Insulin-like growth factor I
/ Insulin-Like Growth Factor I - genetics
/ Insulin-Like Growth Factor I - metabolism
/ Insulin-Like Growth Factor I - physiology
/ Kinases
/ Medical sciences
/ Mice
/ Mice, Inbred C57BL
/ Mice, Knockout
/ Musculoskeletal system
/ Phenotype
/ Physiological aspects
/ Receptor, IGF Type 1 - genetics
/ Receptor, IGF Type 1 - physiology
/ Research design
/ Reverse Transcriptase Polymerase Chain Reaction
/ RNA, Messenger - genetics
/ RNA, Messenger - metabolism
/ Signal Transduction
2008
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Autocrine IGF-1 Action in Adipocytes Controls Systemic IGF-1 Concentrations and Growth
by
Nora Klöting
, Jens C. Brüning
, Thomas Wunderlich
, Matthias Kern
, Linda Koch
, Wilhelm Krone
, Matthias Blüher
, Karen Ruschke
in
Adipocytes
/ Adipocytes - cytology
/ Adipocytes - metabolism
/ Adipose Tissue - cytology
/ Adipose Tissue - metabolism
/ Animals
/ Biological and medical sciences
/ Body fat
/ Body Weight - physiology
/ Cells, Cultured
/ Company growth
/ Diabetes. Impaired glucose tolerance
/ Eating - physiology
/ Endocrine pancreas. Apud cells (diseases)
/ Endocrinopathies
/ Etiopathogenesis. Screening. Investigations. Target tissue resistance
/ Fat cells
/ Gene Deletion
/ Gene Expression
/ Glucose - metabolism
/ Growth
/ Insulin
/ Insulin-like growth factor 1
/ Insulin-Like Growth Factor Binding Protein 3 - blood
/ Insulin-like growth factor I
/ Insulin-Like Growth Factor I - genetics
/ Insulin-Like Growth Factor I - metabolism
/ Insulin-Like Growth Factor I - physiology
/ Kinases
/ Medical sciences
/ Mice
/ Mice, Inbred C57BL
/ Mice, Knockout
/ Musculoskeletal system
/ Phenotype
/ Physiological aspects
/ Receptor, IGF Type 1 - genetics
/ Receptor, IGF Type 1 - physiology
/ Research design
/ Reverse Transcriptase Polymerase Chain Reaction
/ RNA, Messenger - genetics
/ RNA, Messenger - metabolism
/ Signal Transduction
2008
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Autocrine IGF-1 Action in Adipocytes Controls Systemic IGF-1 Concentrations and Growth
Journal Article
Autocrine IGF-1 Action in Adipocytes Controls Systemic IGF-1 Concentrations and Growth
2008
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Overview
Autocrine IGF-1 Action in Adipocytes Controls Systemic IGF-1 Concentrations and Growth
Nora Klöting 1 ,
Linda Koch 2 ,
Thomas Wunderlich 2 ,
Matthias Kern 1 ,
Karen Ruschke 1 ,
Wilhelm Krone 3 ,
Jens C. Brüning 2 and
Matthias Blüher 1 3 4
1 Department of Medicine, University of Leipzig, Leipzig, Germany
2 Department of Mouse Genetics and Metabolism, Institute for Genetics, University of Cologne and Center of Molecular Medicine
Cologne, Cologne, Germany
3 Department of Internal Medicine II, University of Cologne and Center of Molecular Medicine Cologne, Cologne, Germany
4 Interdisciplinary Center for Clinical Research (IZKF), Leipzig, Germany
Corresponding authors: Jens C. Brüning, jens.bruening{at}uni-koeln.de ; Matthias Blüher, bluma{at}medizin.uni-leipzig.de
Abstract
OBJECTIVE— IGF-1 and the IGF-1 receptor (IGF-1R) have been implicated in the regulation of adipocyte differentiation and lipid accumulation
in vitro.
RESEARCH DESIGN AND METHODS— To investigate the role of IGF-1 receptor in vivo, we have inactivated the Igf-1r gene in adipose tissue (IGF-1R aP2Cre mice) using conditional gene targeting strategies.
RESULTS— Conditional IGF-1R inactivation resulted in increased adipose tissue mass with a predominantly increased lipid accumulation
in epigonadal fat pads. However, insulin-stimulated glucose uptake into adipocytes was unaffected by the deletion of the IGF-1R.
Surprisingly, IGF-1R aP2Cre mice exhibited markedly increased somatic growth in the presence of elevated IGF-1 serum concentrations, and IGF-1 mRNA expression
was significantly increased in liver and adipose tissue. IGF-1 stimulation of wild-type adipocytes significantly decreased
IGF-1 mRNA expression, whereas the opposite effect was observed in IGF-1R–deficient adipocytes.
CONCLUSIONS— IGF-1R signaling in adipocytes does not appear to be crucial for the development and differentiation of adipose tissue in
vivo, but we identified a negative IGF-1R–mediated feedback mechanism of IGF-1 on its own gene expression in adipocytes, indicating
an unexpected role for adipose tissue IGF-1 signaling in the regulation of IGF-1 serum concentrations in control of somatic
growth.
Footnotes
Published ahead of print at http://diabetes.diabetesjournals.org on 28 April 2008.
N.K. and L.K. contributed equally to this work.
Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work
is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore
be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Accepted April 22, 2008.
Received October 29, 2007.
DIABETES
Publisher
American Diabetes Association
Subject
/ Animals
/ Biological and medical sciences
/ Body fat
/ Diabetes. Impaired glucose tolerance
/ Endocrine pancreas. Apud cells (diseases)
/ Etiopathogenesis. Screening. Investigations. Target tissue resistance
/ Growth
/ Insulin
/ Insulin-like growth factor 1
/ Insulin-Like Growth Factor Binding Protein 3 - blood
/ Insulin-like growth factor I
/ Insulin-Like Growth Factor I - genetics
/ Insulin-Like Growth Factor I - metabolism
/ Insulin-Like Growth Factor I - physiology
/ Kinases
/ Mice
/ Receptor, IGF Type 1 - genetics
/ Receptor, IGF Type 1 - physiology
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