Link Between GIP and Osteopontin in Adipose Tissue and Insulin Resistance

被引：88

作者：

Ahlqvist, Emma ^{[1
]}

Osmark, Peter ^{[1
]}

Kuulasmaa, Tiina ^{[2
]}

Pilgaard, Kasper ^{[3
]}

Omar, Bilal ^{[4
]}

Brons, Charlotte ^{[3
]}

Kotova, Olga ^{[5
]}

Zetterqvist, Anna V. ^{[5
]}

Stancakova, Alena ^{[6
,7
]}

Jonsson, Anna ^{[1
]}

Hansson, Ola ^{[1
]}

Kuusisto, Johanna ^{[6
,7
]}

Kieffer, Timothy J. ^{[8
,9
]}

Tuomi, Tiinamaija ^{[10
,11
,12
]}

Isomaa, Bo ^{[10
,13
]}

Madsbad, Sten ^{[14
]}

Gomez, Maria F. ^{[5
]}

Poulsen, Pernille ^{[3
]}

Laakso, Markku ^{[6
,7
]}

Degerman, Eva ^{[4
]}

Pihlajamaki, Jussi ^{[2
,6
,7
]}

Wierup, Nils ^{[15
]}

Vaag, Allan ^{[3
,16
,17
]}

Groop, Leif ^{[1
,18
]}

Lyssenko, Valeriya ^{[1
]}

机构：

[1] Lund Univ, Malmo Univ Hosp, Dept Clin Sci Diabet & Endocrinol, Malmo, Sweden

[2] Univ Eastern Finland, Dept Clin Nutr, Kuopio, Finland

[3] Steno Diabet Ctr, DK-2820 Gentofte, Denmark

[4] Lund Univ, Dept Expt Med Sci, Lund, Sweden

[5] Lund Univ, Malmo Univ Hosp, Dept Clin Sci, Vasc ET Coupling, Malmo, Sweden

[6] Univ Eastern Finland, Dept Med, Kuopio, Finland

[7] Kuopio Univ Hosp, SF-70210 Kuopio, Finland

[8] Univ British Columbia, Lab Mol & Cellular Med, Dept Cellular & Physiol Sci, Inst Life Sci, Vancouver, BC V5Z 1M9, Canada

[9] Univ British Columbia, Dept Surg, Vancouver, BC V6T 1W5, Canada

[10] Folkhalsan Res Ctr, Helsinki, Finland

[11] Univ Helsinki, Cent Hosp, Dept Med, Helsinki, Finland

[12] Univ Helsinki, Res Program Mol Med, Helsinki, Finland

[13] Dept Social Serv & Hlth Care, Pietarsaari, Finland

[14] Univ Copenhagen, Hvidovre Hosp, Dept Endocrinol, Copenhagen, Denmark

[15] Lund Univ, Dept Clin Sci, Unit Neuroendocrine Cell Biol, Malmo, Sweden

[16] Rigshosp, Dept Endocrinol, DK-2100 Copenhagen, Denmark

[17] Univ Copenhagen, Copenhagen, Denmark

[18] Univ Helsinki, Finnish Inst Mol Med, Helsinki, Finland

来源：

DIABETES | 2013年 / 62卷 / 06期

基金：

瑞典研究理事会; 芬兰科学院; 欧洲研究理事会;

关键词：

GLUCOSE-TOLERANCE; ORAL GLUCOSE; SENSITIVITY; INFLAMMATION; ADIPOCYTES; RELEASE;

D O I：

10.2337/db12-0976

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

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.

引用

页码：2088 / 2094

页数：7

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