Document Detail

A link between GIP and osteopontin in adipose tissue and insulin resistance.
MedLine Citation:
PMID:  23349498     Owner:  NLM     Status:  Publisher    
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.
Emma Ahlqvist; Peter Osmark; Tiina Kuulasmaa; Kasper Pilgaard; Bilal Omar; Charlotte Brøns; Olga Kotova; Anna V Zetterqvist; Alena Stancáková; Anna Jonsson; Ola Hansson; Johanna Kuusisto; Timothy J Kieffer; Tiinamaija Tuomi; Bo Isomaa; Sten Madsbad; Maria F Gomez; Pernille Poulsen; Markku Laakso; Eva Degerman; Jussi Pihlajamäki; Nils Wierup; Allan Vaag; Leif Groop; Valeriya Lyssenko
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-24
Journal Detail:
Title:  Diabetes     Volume:  -     ISSN:  1939-327X     ISO Abbreviation:  Diabetes     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372763     Medline TA:  Diabetes     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Lund University, Department of Clinical Sciences/Diabetes & Endocrinology, Malmö, Sweden.
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