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Autocrine Action of Adiponectin on Human Fat Cells Prevents the Release of Insulin Resistance-Inducing Factors
Ist Teil von
Diabetes (New York, N.Y.), 2005-07, Vol.54 (7), p.2003-2011
Ort / Verlag
Alexandria, VA: American Diabetes Association
Erscheinungsjahr
2005
Link zum Volltext
Quelle
EZB Free E-Journals
Beschreibungen/Notizen
Autocrine Action of Adiponectin on Human Fat Cells Prevents the Release of Insulin Resistance-Inducing Factors
Daniela Dietze-Schroeder ,
Henrike Sell ,
Mathias Uhlig ,
Marlis Koenen and
Jürgen Eckel
From the Institute of Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Düsseldorf, Germany
Address correspondence and reprint requests to Prof. Dr. Jürgen Eckel, German Diabetes Center, Auf’m Hennekamp 65, D-40225,
Düsseldorf, Germany. E-mail: eckel{at}uni-duesseldorf.de
Abstract
The adipocyte hormone adiponectin is negatively correlated with obesity and insulin resistance and may exert an important
antidiabetes function. In this study, primary human skeletal muscle cells were cocultured with human fat cells or incubated
with adipocyte-conditioned medium in the presence or absence of the globular domain of adiponectin (gAcrp30) to analyze its
capacity to restore normal insulin signaling in the muscle cells. Human skeletal muscle cells cocultured with adipocytes or
treated with adipocyte-conditioned medium showed an impaired Akt and glycogen synthase kinase 3 serine phosphorylation in
response to insulin. Furthermore, insulin-stimulated GLUT4 translocation was reduced by adipocyte-conditioned medium. Impaired
insulin signaling was normalized upon addition of gAcrp30 to the coculture. Further, adipocyte-conditioned medium generated
in the presence of gAcrp30 was unable to perturb insulin-stimulated Akt phosphorylation. Concomitant addition of gAcrp30 and
adipocyte-conditioned medium to the myocytes failed to restore normal insulin action. Protein array analysis of adipocyte-conditioned
medium indicated that the secretion of at least eight different cytokines was diminished in response to gAcrp30. We therefore
suggest that adiponectin operates as a key regulator of adipocyte secretory function. This autocrine action may prevent the
induction of skeletal muscle insulin resistance and may partly explain the antidiabetes action of this hormone.
Acrp30, adipocyte complement-related protein of 30 kDa
gAcrp30, globular domain of Acrp30
GSK, glycogen synthase kinase
GRO, growth-regulated oncogene
HGF, hepatocyte growth factor
HRP, horseradish peroxidase
IGFBP, IGF-binding protein
IL, interleukin
MCP, monocyte chemotactic protein
MIP, macrophage inflammatory protein
sTNFR, soluble TNF receptor
TIMP, tissue inhibitor of metalloproteinase
TNF, tumor necrosis factor
Footnotes
D.D.-S. and H.S. contributed equally to this work.
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 18, 2005.
Received September 28, 2004.
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