Fatty acid-binding protein 4 impairs the insulin-dependent nitric oxide pathway in vascular endothelial cells

Title: Fatty acid-binding protein 4 impairs the insulin-dependent nitric oxide pathway in vascular endothelial cells
Author(s): Aragonès, G
Saavedra, P
Heras, M
Cabré, A
Girona, J
Masana, L
Item Type: Journal Article
Abstract:  BACKGROUND: Recent studies have shown that fatty acid-binding protein 4 (FABP4) plasma levels are associated with impaired endothelial function in type 2 diabetes (T2D). In this work, we analysed the effect of FABP4 on the insulin-mediated nitric oxide (NO) production by endothelial cells in vitro. METHODS: In human umbilical vascular endothelial cells (HUVECs), we measured the effects of FABP4 on the insulin-mediated endothelial nitric oxide synthase (eNOS) expression and activation and on NO production. We also explored the impact of exogenous FABP4 on the insulin-signalling pathway (insulin receptor substrate 1 (IRS1) and Akt). RESULTS: We found that eNOS expression and activation and NO production are significantly inhibited by exogenous FABP4 in HUVECs. FABP4 induced an alteration of the insulin-mediated eNOS pathway by inhibiting IRS1 and Akt activation. These results suggest that FABP4 induces endothelial dysfunction by inhibiting the activation of the insulin-signalling pathway resulting in decreased eNOS activation and NO production. CONCLUSION: These findings provide a mechanistic linkage between FABP4 and impaired endothelial function in diabetes, which leads to an increased cardiovascular risk.
Publication Date: 18-Jun-2012
Date of Acceptance: 18-Jun-2012
URI: http://hdl.handle.net/10044/1/33317
DOI: http://dx.doi.org/10.1186/1475-2840-11-72
ISSN: 1475-2840
Publisher: BioMed Central
Journal / Book Title: Cardiovascular Diabetology
Volume: 11
Copyright Statement: © Aragonès et al. 2012. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: Cells, Cultured
Enzyme Activation
Fatty Acid-Binding Proteins
Gene Expression Regulation, Enzymologic
Human Umbilical Vein Endothelial Cells
Humans
Insulin
Insulin Receptor Substrate Proteins
Nitric Oxide
Nitric Oxide Synthase Type III
Phosphorylation
Proto-Oncogene Proteins c-akt
RNA, Messenger
Signal Transduction
Time Factors
Cells, Cultured
Humans
Nitric Oxide
Insulin
RNA, Messenger
Signal Transduction
Gene Expression Regulation, Enzymologic
Enzyme Activation
Phosphorylation
Time Factors
Fatty Acid-Binding Proteins
Proto-Oncogene Proteins c-akt
Nitric Oxide Synthase Type III
Insulin Receptor Substrate Proteins
Human Umbilical Vein Endothelial Cells
Cardiovascular System & Hematology
1102 Cardiovascular Medicine And Haematology
Publication Status: Published
Article Number: 72
Appears in Collections:Division of Surgery
Division of Cancer
Faculty of Medicine



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