Link Between GIP and Osteopontin in Adipose Tissue and Insulin Resistance

Emma Ahlqvist; Peter Osmark; Tiina Kuulasmaa; Kasper Pilgaard; Bilal Omar; Charlotte Brøns; Olga Kotova; Anna V Zetterqvist; Alena Stancáková; Anna Elisabet 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

doi:10.2337/db12-0976

Link Between GIP and Osteopontin in Adipose Tissue and Insulin Resistance

Emma Ahlqvist, Peter Osmark, Tiina Kuulasmaa, Kasper Pilgaard, Bilal Omar, Charlotte Brøns, Olga Kotova, Anna V Zetterqvist, Alena Stancáková, Anna Elisabet Jonsson, Ola Hansson, Johanna Kuusisto, Timothy J Kieffer, Tiinamaija Tuomi, Bo Isomaa, Sten Madsbad, Maria F Gomez, Pernille Poulsen, Markku Laakso, Eva DegermanJussi Pihlajamäki, Nils Wierup, Allan Vaag, Leif Groop, Valeriya Lyssenko

60 Citations (Scopus)

Abstract

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.

Original language	English
Journal	Diabetes
Volume	62
Issue number	6
Pages (from-to)	2088-94
Number of pages	7
ISSN	0012-1797
DOIs	https://doi.org/10.2337/db12-0976
Publication status	Published - Jun 2013

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Ahlqvist, E., Osmark, P., Kuulasmaa, T., Pilgaard, K., Omar, B., Brøns, C., Kotova, O., Zetterqvist, A. V., Stancáková, A., Jonsson, A. E., Hansson, O., Kuusisto, J., Kieffer, T. J., Tuomi, T., Isomaa, B., Madsbad, S., Gomez, M. F., Poulsen, P., Laakso, M., ... Lyssenko, V. (2013). Link Between GIP and Osteopontin in Adipose Tissue and Insulin Resistance. Diabetes, 62(6), 2088-94. https://doi.org/10.2337/db12-0976

Ahlqvist, E, Osmark, P, Kuulasmaa, T, Pilgaard, K, Omar, B, Brøns, C, Kotova, O, Zetterqvist, AV, Stancáková, A, Jonsson, AE, Hansson, O, Kuusisto, J, Kieffer, TJ, Tuomi, T, Isomaa, B, Madsbad, S, Gomez, MF, Poulsen, P, Laakso, M, Degerman, E, Pihlajamäki, J, Wierup, N, Vaag, A, Groop, L & Lyssenko, V 2013, 'Link Between GIP and Osteopontin in Adipose Tissue and Insulin Resistance', Diabetes, vol. 62, no. 6, pp. 2088-94. https://doi.org/10.2337/db12-0976

@article{14a7b2bd4c7445e984ab8c95f08bb966,

title = "Link Between GIP and Osteopontin in Adipose Tissue and Insulin Resistance",

abstract = "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.",

author = "Emma Ahlqvist and Peter Osmark and Tiina Kuulasmaa and Kasper Pilgaard and Bilal Omar and Charlotte Br{\o}ns and Olga Kotova and Zetterqvist, {Anna V} and Alena Stanc{\'a}kov{\'a} and Jonsson, {Anna Elisabet} and Ola Hansson and Johanna Kuusisto and Kieffer, {Timothy J} and Tiinamaija Tuomi and Bo Isomaa and Sten Madsbad and Gomez, {Maria F} and Pernille Poulsen and Markku Laakso and Eva Degerman and Jussi Pihlajam{\"a}ki and Nils Wierup and Allan Vaag and Leif Groop and Valeriya Lyssenko",

year = "2013",

month = jun,

doi = "10.2337/db12-0976",

language = "English",

volume = "62",

pages = "2088--94",

journal = "Diabetes",

issn = "0012-1797",

publisher = "American Diabetes Association",

number = "6",

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T1 - Link Between GIP and Osteopontin in Adipose Tissue and Insulin Resistance

AU - Ahlqvist, Emma

AU - Osmark, Peter

AU - Kuulasmaa, Tiina

AU - Pilgaard, Kasper

AU - Omar, Bilal

AU - Brøns, Charlotte

AU - Kotova, Olga

AU - Zetterqvist, Anna V

AU - Stancáková, Alena

AU - Jonsson, Anna Elisabet

AU - Hansson, Ola

AU - Kuusisto, Johanna

AU - Kieffer, Timothy J

AU - Tuomi, Tiinamaija

AU - Isomaa, Bo

AU - Madsbad, Sten

AU - Gomez, Maria F

AU - Poulsen, Pernille

AU - Laakso, Markku

AU - Degerman, Eva

AU - Pihlajamäki, Jussi

AU - Wierup, Nils

AU - Vaag, Allan

AU - Groop, Leif

AU - Lyssenko, Valeriya

PY - 2013/6

Y1 - 2013/6

N2 - 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.

AB - 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.

U2 - 10.2337/db12-0976

DO - 10.2337/db12-0976

M3 - Journal article

C2 - 23349498

SN - 0012-1797

VL - 62

SP - 2088

EP - 2094

JO - Diabetes

JF - Diabetes

IS - 6

ER -

Link Between GIP and Osteopontin in Adipose Tissue and Insulin Resistance

Abstract

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