Autocrine IGF-1 Action in Adipocytes Controls Systemic IGF-1 Concentrations and Growth
| Autor: | Matthias Kern, Nora Klöting, Matthias Blüher, Karen Ruschke, Jens C. Brüning, Thomas F. Wunderlich, Wilhelm Krone, Linda Koch |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
medicine.medical_specialty
FGF21 Endocrinology Diabetes and Metabolism Adipose tissue macrophages Glucose uptake Gene Expression Adipose tissue White adipose tissue Biology Receptor IGF Type 1 Eating Mice chemistry.chemical_compound Adipocyte Internal medicine Adipocytes Internal Medicine medicine Animals RNA Messenger Insulin-Like Growth Factor I Autocrine signalling Cells Cultured Mice Knockout Reverse Transcriptase Polymerase Chain Reaction Body Weight Mice Inbred C57BL Glucose Insulin-Like Growth Factor Binding Protein 3 Phenotype Endocrinology Adipose Tissue chemistry Adipogenesis Gene Deletion Signal Transduction |
| Zdroj: | Diabetes |
| ISSN: | 1939-327X 0012-1797 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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