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

Summary, in English

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.

• Författare: Emma Ahlqvist; Peter Osmark; Tiina Kuulasmaa; Kasper Pilgaard; Bilal Omar; Charlotte Brøns; Olga Kotova; Anna 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
• Avdelning/ar: Translationell Muskel Forskning; Medicin/akutsjukvård, Lund; Diabetiska komplikationer; Signaltransduktionsforskning; Institutionen för experimentell medicinsk vetenskap; EXODIAB: Excellence of Diabetes Research in Sweden; EpiHealth: Epidemiology for Health
• Publiceringsår: 2013
• Språk: Engelska
• Sidor: 2088-2094
• Publikation/Tidskrift/Serie: Diabetes
• Volym: 62
• Issue: 6
• Länkar: http://www.ncbi.nlm.nih.gov/pubmed/23349498?dopt=Abstract; http://dx.doi.org/10.2337/db12-0976
• Dokumenttyp: Artikel i tidskrift
• Förlag: American Diabetes Association Inc.
• Ämne: Endocrinology and Diabetes
• Status: Published
• Forskningsgrupp: Genomics, Diabetes and Endocrinology; Diabetic Complications; Insulin Signal Transduction
• ISBN/ISSN/Övrigt: ISSN: 1939-327X