PT  - JOURNAL ARTICLE
AU  - Ahlqvist, Emma
AU  - Osmark, Peter
AU  - Kuulasmaa, Tiina
AU  - Pilgaard, Kasper
AU  - Omar, Bilal
AU  - Brøns, Charlotte
AU  - Kotova, Olga
AU  - Zetterqvist, Anna V.
AU  - Stančáková, Alena
AU  - Jonsson, Anna
AU  - Hansson, Ola
AU  - Kuusisto, Johanna
AU  - Kieffer, Timothy J.
AU  - Tuomi, Tiinamaija
AU  - Isomaa, Bo
AU  - Madsbad, Sten
AU  - Gomez, Maria F.
AU  - Poulsen, Pernille
AU  - Laakso, Markku
AU  - Degerman, Eva
AU  - Pihlajamäki, Jussi
AU  - Wierup, Nils
AU  - Vaag, Allan
AU  - Groop, Leif
AU  - Lyssenko, Valeriya
TI  - Link Between GIP and Osteopontin in Adipose Tissue and Insulin Resistance
AID  - 10.2337/db12-0976
DP  - 2013 Jun 01
TA  - Diabetes
PG  - 2088--2094
VI  - 62
IP  - 6
4099  - http://diabetes.diabetesjournals.org/content/62/6/2088.short
4100  - http://diabetes.diabetesjournals.org/content/62/6/2088.full
SO  - Diabetes2013 Jun 01; 62
AB  - Low-grade inflammation in obesity is associated with accumulation of the macrophage-derived cytokine osteopontin (OPN) in adipose tissue and induction of local as well as systemic insulin resistance. Since glucose-dependent insulinotropic polypeptide (GIP) is a strong stimulator of adipogenesis and may play a role in the development of obesity, we explored whether GIP directly would stimulate 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 a 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 the 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.