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A link between GIP and osteopontin in adipose tissue and insulin resistance.

Ahlqvist, Emma LU ; Osmark, Peter LU ; Kuulasmaa, Tiina; Pilgaard, Kasper; Omar, Bilal LU ; Brøns, Charlotte; Kotova, Olga LU ; Zetterqvist, Anna LU ; Stancáková, Alena and Jonsson, Anna LU , et al. (2013) In Diabetes 62(6). p.2088-2094
Abstract
Low grade inflammation in obesity is associated with accumulation of the macrophagederived cytokine osteopontin in adipose tissue and induction of local as well as systemic insulin resistance. Since GIP (glucose-dependent insulinotropic polypeptide) is a strong stimulator of adipogenesis and may play a role in the development of obesity, we explored whether GIP directly would stimulate osteopontin (OPN) expression in adipose tissue and thereby induce insulin resistance. GIP stimulated OPN protein expression in a dose-dependent fashion in rat primary adipocytes. The level of OPN mRNA was higher in adipose tissue of obese individuals (0.13±}0.04 vs 0.04±}0.01, P<0.05) and correlated inversely with measures of insulin sensitivity (r=-0.24,... (More)
Low grade inflammation in obesity is associated with accumulation of the macrophagederived cytokine osteopontin in adipose tissue and induction of local as well as systemic insulin resistance. Since GIP (glucose-dependent insulinotropic polypeptide) is a strong stimulator of adipogenesis and may play a role in the development of obesity, we explored whether GIP directly would stimulate osteopontin (OPN) expression in adipose tissue and thereby induce insulin resistance. GIP stimulated OPN protein expression in a dose-dependent fashion in rat primary adipocytes. The level of OPN mRNA was higher in adipose tissue of obese individuals (0.13±}0.04 vs 0.04±}0.01, P<0.05) and correlated inversely with measures of insulin sensitivity (r=-0.24, P=0.001). A common variant of the GIP receptor (GIPR) (rs10423928) gene was associated with lower amount of the exon 9 containing isoform required for transmembrane activity. Carriers of the A-allele with a reduced receptor function showed lower adipose tissue OPN mRNA levels and better insulin sensitivity. Together, these data suggest a role for GIP not only as an incretin hormone, but also as a trigger of inflammation and insulin resistance in adipose tissue. Carriers of GIPR rs10423928 A-allele showed protective properties via reduced GIP effects. Identification of this unprecedented link between GIP and OPN in adipose tissue might open new avenues for therapeutic interventions. (Less)
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Contribution to journal
publication status
published
subject
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Diabetes
volume
62
issue
6
pages
2088 - 2094
publisher
American Diabetes Association Inc.
external identifiers
  • wos:000319845000039
  • pmid:23349498
  • scopus:84878250644
ISSN
1939-327X
DOI
10.2337/db12-0976
language
English
LU publication?
yes
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ac1031b5-93ba-4bcc-aee4-80f618c0a647 (old id 3438299)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/23349498?dopt=Abstract
date added to LUP
2013-02-04 17:06:25
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2019-05-14 01:38:37
@article{ac1031b5-93ba-4bcc-aee4-80f618c0a647,
  abstract     = {Low grade inflammation in obesity is associated with accumulation of the macrophagederived cytokine osteopontin in adipose tissue and induction of local as well as systemic insulin resistance. Since GIP (glucose-dependent insulinotropic polypeptide) is a strong stimulator of adipogenesis and may play a role in the development of obesity, we explored whether GIP directly would stimulate osteopontin (OPN) expression in adipose tissue and thereby induce insulin resistance. GIP stimulated OPN protein expression in a dose-dependent fashion in rat primary adipocytes. The level of OPN mRNA was higher in adipose tissue of obese individuals (0.13±}0.04 vs 0.04±}0.01, P&lt;0.05) and correlated inversely with measures of insulin sensitivity (r=-0.24, P=0.001). A common variant of the GIP receptor (GIPR) (rs10423928) gene was associated with lower amount of the exon 9 containing isoform required for transmembrane activity. Carriers of the A-allele with a reduced receptor function showed lower adipose tissue OPN mRNA levels and better insulin sensitivity. Together, these data suggest a role for GIP not only as an incretin hormone, but also as a trigger of inflammation and insulin resistance in adipose tissue. Carriers of GIPR rs10423928 A-allele showed protective properties via reduced GIP effects. Identification of this unprecedented link between GIP and OPN in adipose tissue might open new avenues for therapeutic interventions.},
  author       = {Ahlqvist, Emma and Osmark, Peter and Kuulasmaa, Tiina and Pilgaard, Kasper and Omar, Bilal and Brøns, Charlotte and Kotova, Olga and Zetterqvist, Anna and Stancáková, Alena and Jonsson, Anna and Hansson, Ola and Kuusisto, Johanna and Kieffer, Timothy J and Tuomi, Tiinamaija and Isomaa, Bo and Madsbad, Sten and Gomez, Maria F and Poulsen, Pernille and Laakso, Markku and Degerman, Eva and Pihlajamäki, Jussi and Wierup, Nils and Vaag, Allan and Groop, Leif and Lyssenko, Valeriya},
  issn         = {1939-327X},
  language     = {eng},
  number       = {6},
  pages        = {2088--2094},
  publisher    = {American Diabetes Association Inc.},
  series       = {Diabetes},
  title        = {A link between GIP and osteopontin in adipose tissue and insulin resistance.},
  url          = {http://dx.doi.org/10.2337/db12-0976},
  volume       = {62},
  year         = {2013},
}