Journal
DIABETES
Volume 62, Issue 6, Pages 2088-2094Publisher
AMER DIABETES ASSOC
DOI: 10.2337/db12-0976
Keywords
-
Categories
Funding
- Linnaeus grant (LUDC) [349-2008-6589]
- Swedish Research Council [521-2007-4037, 521-2010-2633]
- strategic research area grant (EXODIAB) [2009-1039]
- European Research Council [GA 269045]
- Wallenberg [KAW 2009-0243]
- Lundberg Foundation [359]
- Novo Nordisk
- Ahlen
- Ake Wiberg
- Magnus Bergwall
- Tore Nilsson
- Fredrik
- Ingrid Thuring
- Crafoord
- Albert Pahlsson
- Lars Hierta Memorial
- Royal Physiographic Society
- Foundation of the National Board of Health and Welfare
- Malmo University Hospital
- European Foundation for the Study of Diabetes
- Academy of Finland
- Finnish Diabetes Research Foundation
- European Union grant ENGAGE
- Novo Nordisk Fonden [NNF12OC1016467] Funding Source: researchfish
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available