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Horm Metab Res 2012; 44(07): 501-505
DOI: 10.1055/s-0032-1312595
Original Basic
© Georg Thieme Verlag KG Stuttgart · New York

Glucose-dependent Insulinotropic Polypeptide (GIP) Inhibits Signaling Pathways of Advanced Glycation End Products (AGEs) in Endothelial Cells via its Antioxidative Properties

A. Ojima
1   Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Japan
,
T. Matsui
1   Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Japan
,
S. Maeda
1   Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Japan
,
M. Takeuchi
2   Department of Advanced Medicine, Medical Research Institute, Kanazawa Medical University, Kanazawa, Japan
,
S. Yamagishi
1   Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Japan
› Author Affiliations
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Publication History

received 12 November 2011

accepted 04 October 2012

Publication Date:
11 May 2012 (online)

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Abstract

Glucose-dependent insulinotropic polypeptide (GIP) is one of the incretins, a gut hormone secreted from K cells in the intestine in response to food intake. It could be a potential therapeutic target for the treatment of patients with type 2 diabetes. However, effects of GIP on vascular injury remain unknown. Since interaction of advanced glycation end products (AGEs) with their receptor RAGE has been shown to play a crucial role in vascular damage in diabetes, this study investigated whether and how GIP blocked the deleterious effects of AGEs on human umbilical vein endothelial cells (HUVECs). GIP receptor was expressed in HUVECs. GIP, an analogue of cyclic AMP or inhibitors of NADPH oxidase inhibited the AGE-induced reactive oxygen species (ROS) generation in HUVECs. Furthermore, GIP reduced both RAGE mRNA and protein levels in HUVECs. GLP-1 also blocked the AGE-induced increase in mRNA levels of vascular cell adhesion molecule-1 (VCAM-1) and plasminogen activator inhibitor-1 in HUVECs. In addition, an antioxidant N-acetylcysteine mimicked the effects of GIP on RAGE and VCAM-1 gene expression in HUVECs. Our present study suggests that GIP could block the signal pathways of AGEs in HUVECs by reducing ROS generation and subsequent RAGE expression probably via GIP receptor-cyclic AMP axis.

Key words

AGEs - vascular injury - cAMP - GIP - RAGE
 

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