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Published online April 28, 2008
Diabetes 57:2074-2082, 2008
DOI: 10.2337/db07-1538
© 2008 by the American Diabetes Association
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Autocrine IGF-1 Action in Adipocytes Controls Systemic IGF-1 Concentrations and Growth

Nora Klöting1, Linda Koch2, Thomas Wunderlich2, Matthias Kern1, Karen Ruschke1, Wilhelm Krone3, Jens C. Brüning2, and Matthias Blüher1,3,4

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

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-1RaP2Cre 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-1RaP2Cre 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.


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