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Glucose-Dependent Insulinotropic Polypeptide (GIP) Stimulates Osteopontin Expression in the Vasculature via Endothelin-1 and CREB.

Berglund, Lisa LU ; Lyssenko, Valeriya LU ; Ladenvall, Claes LU ; Kotova, Olga LU ; Edsfeldt, Andreas LU ; Pilgaard, Kasper; Alkayyali, Sami LU ; Brøns, Charlotte; Forsblom, Carol and Jonsson, Anna LU , et al. (2016) In Diabetes 65(1). p.239-254
Abstract
Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone with extrapancreatic effects beyond glycemic control. Here we demonstrate unexpected effects of GIP signaling in the vasculature. GIP induces the expression of the pro-atherogenic cytokine osteopontin (OPN) in mouse arteries, via local release of endothelin-1 (ET-1) and activation of cAMP response element binding protein (CREB). Infusion of GIP increases plasma OPN levels in healthy individuals. Plasma ET-1 and OPN levels are positively correlated in patients with critical limb ischemia. Fasting GIP levels are higher in individuals with a history of cardiovascular disease (myocardial infarction, stroke) when compared to controls. GIP receptor (GIPR) and OPN mRNA... (More)
Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone with extrapancreatic effects beyond glycemic control. Here we demonstrate unexpected effects of GIP signaling in the vasculature. GIP induces the expression of the pro-atherogenic cytokine osteopontin (OPN) in mouse arteries, via local release of endothelin-1 (ET-1) and activation of cAMP response element binding protein (CREB). Infusion of GIP increases plasma OPN levels in healthy individuals. Plasma ET-1 and OPN levels are positively correlated in patients with critical limb ischemia. Fasting GIP levels are higher in individuals with a history of cardiovascular disease (myocardial infarction, stroke) when compared to controls. GIP receptor (GIPR) and OPN mRNA levels are higher in carotid endarterectomies from patients with symptoms (stroke, transient ischemic attacks, amaurosis fugax) than in asymptomatic patients; and expression associates to parameters characteristic of unstable and inflammatory plaques (increased lipid accumulation, macrophage infiltration and reduced smooth muscle cell content). While GIPR expression is predominantly endothelial in healthy arteries from human, mouse, rat and pig; remarkable up-regulation is observed in endothelial and smooth muscle cells upon culture conditions yielding a "vascular disease-like" phenotype. Moreover, a common variant rs10423928 in the GIPR gene associated with increased risk of stroke in type 2 diabetes patients. (Less)
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Contribution to journal
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published
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Diabetes
volume
65
issue
1
pages
239 - 254
publisher
American Diabetes Association Inc.
external identifiers
  • pmid:26395740
  • wos:000367424900026
  • scopus:84962187932
ISSN
1939-327X
DOI
10.2337/db15-0122
language
English
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yes
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e67b2fbf-eef6-4a67-af3f-09ab1c80efde (old id 8035204)
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http://www.ncbi.nlm.nih.gov/pubmed/26395740?dopt=Abstract
date added to LUP
2015-10-03 16:37:44
date last changed
2017-11-05 03:26:28
@article{e67b2fbf-eef6-4a67-af3f-09ab1c80efde,
  abstract     = {Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone with extrapancreatic effects beyond glycemic control. Here we demonstrate unexpected effects of GIP signaling in the vasculature. GIP induces the expression of the pro-atherogenic cytokine osteopontin (OPN) in mouse arteries, via local release of endothelin-1 (ET-1) and activation of cAMP response element binding protein (CREB). Infusion of GIP increases plasma OPN levels in healthy individuals. Plasma ET-1 and OPN levels are positively correlated in patients with critical limb ischemia. Fasting GIP levels are higher in individuals with a history of cardiovascular disease (myocardial infarction, stroke) when compared to controls. GIP receptor (GIPR) and OPN mRNA levels are higher in carotid endarterectomies from patients with symptoms (stroke, transient ischemic attacks, amaurosis fugax) than in asymptomatic patients; and expression associates to parameters characteristic of unstable and inflammatory plaques (increased lipid accumulation, macrophage infiltration and reduced smooth muscle cell content). While GIPR expression is predominantly endothelial in healthy arteries from human, mouse, rat and pig; remarkable up-regulation is observed in endothelial and smooth muscle cells upon culture conditions yielding a "vascular disease-like" phenotype. Moreover, a common variant rs10423928 in the GIPR gene associated with increased risk of stroke in type 2 diabetes patients.},
  author       = {Berglund, Lisa and Lyssenko, Valeriya and Ladenvall, Claes and Kotova, Olga and Edsfeldt, Andreas and Pilgaard, Kasper and Alkayyali, Sami and Brøns, Charlotte and Forsblom, Carol and Jonsson, Anna and Zetterqvist, Anna and Nitulescu, Mihaela and Ruiz McDavitt, Christian and Dunér, Pontus and Stancáková, Alena and Kuusisto, Johanna and Ahlqvist, Emma and Lajer, Maria and Tarnow, Lise and Madsbad, Sten and Rossing, Peter and Kieffer, Timothy J and Melander, Olle and Orho-Melander, Marju and Nilsson, Peter and Groop, Per-Henrik and Vaag, Allan and Lindblad, Bengt and Gottsäter, Anders and Laakso, Markku and Goncalves, Isabel and Groop, Leif and Gomez, Maria},
  issn         = {1939-327X},
  language     = {eng},
  number       = {1},
  pages        = {239--254},
  publisher    = {American Diabetes Association Inc.},
  series       = {Diabetes},
  title        = {Glucose-Dependent Insulinotropic Polypeptide (GIP) Stimulates Osteopontin Expression in the Vasculature via Endothelin-1 and CREB.},
  url          = {http://dx.doi.org/10.2337/db15-0122},
  volume       = {65},
  year         = {2016},
}