Link Between GIP and Osteopontin in Adipose Tissue and Insulin Resistance
| Autor: | Peter Osmark, Bilal Omar, Leif Groop, Alena Stančáková, Tiina Kuulasmaa, Emma Ahlqvist, Kasper Pilgaard, Bo Isomaa, Valeriya Lyssenko, Nils Wierup, Eva Degerman, Jussi Pihlajamäki, Tiinamaija Tuomi, Allan Vaag, Johanna Kuusisto, Anna Jonsson, Olga Kotova, Maria F. Gomez, Sten Madsbad, Ola Hansson, Pernille Poulsen, Anna V. Zetterqvist, Timothy J. Kieffer, Charlotte Brøns, Markku Laakso |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Adult
Male endocrine system medicine.medical_specialty Adolescent Endocrinology Diabetes and Metabolism Adipose tissue 030209 endocrinology & metabolism Inflammation Gastric Inhibitory Polypeptide In Vitro Techniques Biology Pathophysiology Receptors Gastrointestinal Hormone Mice Young Adult 03 medical and health sciences 0302 clinical medicine Insulin resistance Gastric inhibitory polypeptide stomatognathic system Internal medicine Internal Medicine medicine Animals Humans Osteopontin Receptor Alleles Cells Cultured Original Research Aged 030304 developmental biology 0303 health sciences Middle Aged medicine.disease Rats Endocrinology Adipose Tissue Gastrointestinal hormone Adipogenesis biology.protein Female Insulin Resistance medicine.symptom hormones hormone substitutes and hormone antagonists |
| Zdroj: | Diabetes; Vol 62 Diabetes |
| ISSN: | 0012-1797 |
| DOI: | 10.2337/db12-0976 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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