Autocrine Action of Adiponectin on Human Fat Cells Prevents the Release of Insulin Resistance-Inducing Factors

  1. Daniela Dietze-Schroeder,
  2. Henrike Sell,
  3. Mathias Uhlig,
  4. Marlis Koenen and
  5. Jürgen Eckel
  1. From the Institute of Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Düsseldorf, Germany
  1. 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.

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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