Glucose-dependent insulinotropic polypeptide (GIP) inhibits signaling pathways of advanced glycation end products (AGEs) in endothelial cells via its antioxidative properties

Hormone and Metabolic Research = Hormon- Und Stoffwechselforschung = Hormones Et Métabolisme
A OjimaSho-ichi Yamagishi

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 subsequ...Continue Reading

Citations

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Mar 3, 2015·Laboratory Investigation; a Journal of Technical Methods and Pathology·Takanori MatsuiSho-ichi Yamagishi
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Feb 27, 2020·International Journal of Molecular Sciences·Yusaku MoriSho-Ichi Yamagishi
Aug 21, 2020·Obesity Reviews : an Official Journal of the International Association for the Study of Obesity·Daniela Rosendo-Silva, Paulo Matafome
Jul 11, 2020·International Journal of Molecular Sciences·Michishige TerasakiSho-Ichi Yamagishi
May 1, 2021·International Journal of Molecular Sciences·Rosaria Vincenza GiglioManfredi Rizzo
Jul 27, 2021·Diabetes, Obesity & Metabolism·Michael A NauckAndreas F H Pfeiffer

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