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Regulation of the pro-inflammatory cytokine osteopontin by GIP in adipocytes - A role for the transcription factor NFAT and phosphodiesterase 3B.

Author:
  • Bilal Omar
  • Elin Banke
  • Emilia Guiguis
  • Lina Kesson
  • Vincent Manganiello
  • Valeriya Lyssenko
  • Leif Groop
  • Maria Gomez
  • Eva Degerman
Publishing year: 2012
Language: English
Pages: 812-817
Publication/Series: Biochemical and Biophysical Research Communications
Volume: 425
Issue: 4
Document type: Journal article
Publisher: Elsevier

Abstract english

The incretin - glucose-dependent insulinotropic polypeptide (GIP) - and the pro-inflammatory cytokine osteopontin are known to have important roles in the regulation of adipose tissue functions. In this work we show that GIP stimulates lipogenesis and osteopontin expression in primary adipocytes. The GIP-induced increase in osteopontin expression was inhibited by the NFAT (the transcription factor nuclear factor of activated T-cells) inhibitor A285222. Also, the NFAT kinase glycogen synthase kinase (GSK) 3 was upregulated by GIP. To test whether cAMP might be involved in GIP mediated effects on osteopontin a number of strategies were used. Thus, the β3-adrenergic receptor aganist CL316,243 stimulated osteopontin expression, an effects which was mimicked by OPC3911, a specific inhibitor of phosphodiesterase 3. Furthermore, treatment of phosphodiesterase 3B knock-out mice with CL316,243 resulted in a dramatic upregulation of osteopontin in adipose tissue which was not the case in wild-type mice. In summary, we delineate mechanisms by which GIP stimulate osteopontin in adipocytes. Given the established link between osteopontin and insulin resistance, our data suggest that GIP by stimulating osteopontin expression, also could promote insulin resistance in adipocytes.

Keywords

  • Biological Sciences

Other

Published
  • Insulin Signal Transduction
  • Diabetes and Endocrinology
  • ISSN: 1090-2104
Eva Degerman
E-mail: eva.degerman [at] med.lu.se

Professor

Insulin Signal Transduction

+46 46 222 85 83

+46 70 885 83 62

BMC C1121b

66

Lund University Diabetes Centre, CRC, SUS Malmö, Entrance 72, House 91:12. SE-205 02 Malmö. Telephone: +46 40 39 10 00