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A link between GIP and osteopontin in adipose tissue and insulin resistance.
MedLine Citation:
PMID:  23349498     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.
Authors:
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:  -    
Affiliation:
Lund University, Department of Clinical Sciences/Diabetes & Endocrinology, Malmö, Sweden.
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