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Link Between GIP and Osteopontin in Adipose Tissue and Insulin Resistance
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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Diabetes Association
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3661641/ https://www.ncbi.nlm.nih.gov/pubmed/23349498 http://dx.doi.org/10.2337/db12-0976 |
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author | Ahlqvist, Emma Osmark, Peter Kuulasmaa, Tiina Pilgaard, Kasper Omar, Bilal Brøns, Charlotte Kotova, Olga Zetterqvist, Anna V. Stančáková, Alena Jonsson, Anna Hansson, Ola Kuusisto, Johanna Kieffer, Timothy J. Tuomi, Tiinamaija Isomaa, Bo Madsbad, Sten Gomez, Maria F. Poulsen, Pernille Laakso, Markku Degerman, Eva Pihlajamäki, Jussi Wierup, Nils Vaag, Allan Groop, Leif Lyssenko, Valeriya |
author_facet | Ahlqvist, Emma Osmark, Peter Kuulasmaa, Tiina Pilgaard, Kasper Omar, Bilal Brøns, Charlotte Kotova, Olga Zetterqvist, Anna V. Stančáková, Alena Jonsson, Anna Hansson, Ola Kuusisto, Johanna Kieffer, Timothy J. Tuomi, Tiinamaija Isomaa, Bo Madsbad, Sten Gomez, Maria F. Poulsen, Pernille Laakso, Markku Degerman, Eva Pihlajamäki, Jussi Wierup, Nils Vaag, Allan Groop, Leif Lyssenko, Valeriya |
author_sort | Ahlqvist, Emma |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3661641 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-36616412014-06-01 Link Between GIP and Osteopontin in Adipose Tissue and Insulin Resistance Ahlqvist, Emma Osmark, Peter Kuulasmaa, Tiina Pilgaard, Kasper Omar, Bilal Brøns, Charlotte Kotova, Olga Zetterqvist, Anna V. Stančáková, Alena Jonsson, Anna Hansson, Ola Kuusisto, Johanna Kieffer, Timothy J. Tuomi, Tiinamaija Isomaa, Bo Madsbad, Sten Gomez, Maria F. Poulsen, Pernille Laakso, Markku Degerman, Eva Pihlajamäki, Jussi Wierup, Nils Vaag, Allan Groop, Leif Lyssenko, Valeriya Diabetes Original Research 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. American Diabetes Association 2013-06 2013-05-17 /pmc/articles/PMC3661641/ /pubmed/23349498 http://dx.doi.org/10.2337/db12-0976 Text en © 2013 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details. |
spellingShingle | Original Research Ahlqvist, Emma Osmark, Peter Kuulasmaa, Tiina Pilgaard, Kasper Omar, Bilal Brøns, Charlotte Kotova, Olga Zetterqvist, Anna V. Stančáková, Alena Jonsson, Anna Hansson, Ola Kuusisto, Johanna Kieffer, Timothy J. Tuomi, Tiinamaija Isomaa, Bo Madsbad, Sten Gomez, Maria F. Poulsen, Pernille Laakso, Markku Degerman, Eva Pihlajamäki, Jussi Wierup, Nils Vaag, Allan Groop, Leif Lyssenko, Valeriya Link Between GIP and Osteopontin in Adipose Tissue and Insulin Resistance |
title | Link Between GIP and Osteopontin in Adipose Tissue and Insulin Resistance |
title_full | Link Between GIP and Osteopontin in Adipose Tissue and Insulin Resistance |
title_fullStr | Link Between GIP and Osteopontin in Adipose Tissue and Insulin Resistance |
title_full_unstemmed | Link Between GIP and Osteopontin in Adipose Tissue and Insulin Resistance |
title_short | Link Between GIP and Osteopontin in Adipose Tissue and Insulin Resistance |
title_sort | link between gip and osteopontin in adipose tissue and insulin resistance |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3661641/ https://www.ncbi.nlm.nih.gov/pubmed/23349498 http://dx.doi.org/10.2337/db12-0976 |
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