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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.

Omar, Bilal LU ; Banke, Elin LU ; Guiguis, Emilia; Kesson, Lina; Manganiello, Vincent; Lyssenko, Valeriya LU ; Groop, Leif LU ; Gomez, Maria LU and Degerman, Eva LU (2012) In Biochemical and Biophysical Research Communications 425(4). p.812-817
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Biochemical and Biophysical Research Communications
volume
425
issue
4
pages
812 - 817
publisher
Elsevier
external identifiers
  • wos:000309017700020
  • pmid:22892131
  • scopus:84865991405
ISSN
1090-2104
DOI
10.1016/j.bbrc.2012.07.157
language
English
LU publication?
yes
id
9a6d1ef4-625f-4198-9fb0-d062071ed22e (old id 3047510)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22892131?dopt=Abstract
date added to LUP
2012-09-05 19:38:35
date last changed
2017-01-01 06:04:51
@article{9a6d1ef4-625f-4198-9fb0-d062071ed22e,
  abstract     = {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.},
  author       = {Omar, Bilal and Banke, Elin and Guiguis, Emilia and Kesson, Lina and Manganiello, Vincent and Lyssenko, Valeriya and Groop, Leif and Gomez, Maria and Degerman, Eva},
  issn         = {1090-2104},
  language     = {eng},
  number       = {4},
  pages        = {812--817},
  publisher    = {Elsevier},
  series       = {Biochemical and Biophysical Research Communications},
  title        = {Regulation of the pro-inflammatory cytokine osteopontin by GIP in adipocytes - A role for the transcription factor NFAT and phosphodiesterase 3B.},
  url          = {http://dx.doi.org/10.1016/j.bbrc.2012.07.157},
  volume       = {425},
  year         = {2012},
}