Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2013
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
_version_ 1782270719529320448
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
work_keys_str_mv AT ahlqvistemma linkbetweengipandosteopontininadiposetissueandinsulinresistance
AT osmarkpeter linkbetweengipandosteopontininadiposetissueandinsulinresistance
AT kuulasmaatiina linkbetweengipandosteopontininadiposetissueandinsulinresistance
AT pilgaardkasper linkbetweengipandosteopontininadiposetissueandinsulinresistance
AT omarbilal linkbetweengipandosteopontininadiposetissueandinsulinresistance
AT brønscharlotte linkbetweengipandosteopontininadiposetissueandinsulinresistance
AT kotovaolga linkbetweengipandosteopontininadiposetissueandinsulinresistance
AT zetterqvistannav linkbetweengipandosteopontininadiposetissueandinsulinresistance
AT stancakovaalena linkbetweengipandosteopontininadiposetissueandinsulinresistance
AT jonssonanna linkbetweengipandosteopontininadiposetissueandinsulinresistance
AT hanssonola linkbetweengipandosteopontininadiposetissueandinsulinresistance
AT kuusistojohanna linkbetweengipandosteopontininadiposetissueandinsulinresistance
AT kieffertimothyj linkbetweengipandosteopontininadiposetissueandinsulinresistance
AT tuomitiinamaija linkbetweengipandosteopontininadiposetissueandinsulinresistance
AT isomaabo linkbetweengipandosteopontininadiposetissueandinsulinresistance
AT madsbadsten linkbetweengipandosteopontininadiposetissueandinsulinresistance
AT gomezmariaf linkbetweengipandosteopontininadiposetissueandinsulinresistance
AT poulsenpernille linkbetweengipandosteopontininadiposetissueandinsulinresistance
AT laaksomarkku linkbetweengipandosteopontininadiposetissueandinsulinresistance
AT degermaneva linkbetweengipandosteopontininadiposetissueandinsulinresistance
AT pihlajamakijussi linkbetweengipandosteopontininadiposetissueandinsulinresistance
AT wierupnils linkbetweengipandosteopontininadiposetissueandinsulinresistance
AT vaagallan linkbetweengipandosteopontininadiposetissueandinsulinresistance
AT groopleif linkbetweengipandosteopontininadiposetissueandinsulinresistance
AT lyssenkovaleriya linkbetweengipandosteopontininadiposetissueandinsulinresistance