Autocrine IGF-1 action in adipocytes controls systemic IGF-1 concentrations and growth

被引：109

作者：

Kloeting, Nora ^{[2
]}

Koch, Linda ^{[1
,3
]}

Wunderlich, Thomas ^{[1
,3
]}

Kern, Matthias ^{[2
]}

Ruschke, Karen ^{[2
]}

Krone, Wilhelm ^{[3
,4
]}

Bruening, Jens C. ^{[1
,3
]}

Blueher, Matthias ^{[2
,3
,4
,5
]}

机构：

[1] Univ Cologne, Inst Genet, Dept Mouse Genet & Metab, D-5000 Cologne, Germany

[2] Univ Leipzig, Dept Med, Leipzig, Germany

[3] Ctr Mol Med Cologne, Cologne, Germany

[4] Univ Cologne, Dept Internal Med 2, Cologne, Germany

[5] Interdisciplinary Ctr Clin Res IZKF, Leipzig, Germany

来源：

DIABETES | 2008年 / 57卷 / 08期

关键词：

D O I：

10.2337/db07-1538

中图分类号：

R5 [内科学];

学科分类号：

1002 [临床医学]; 100201 [内科学];

摘要：

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-IR-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-IR-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.

引用

页码：2074 / 2082

页数：9

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