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Mediators of Inflammation
Volume 2014, Article ID 923120, 8 pages
Research Article

Glucagon-Like Peptide-1 Secreting Cell Function as well as Production of Inflammatory Reactive Oxygen Species Is Differently Regulated by Glycated Serum and High Levels of Glucose

1Department of Internal Medicine, University of Genoa School of Medicine, IRCCS Azienda Ospedaliera Universitaria San Martino, IST Istituto Nazionale per la Ricerca sul Cancro, 6 Viale Benedetto XV, 16143 Genoa, Italy
2Division of Cardiology, Department of Medicine, Geneva University Hospitals, Faculty of Medicine, Foundation for Medical Researches, 64 Avenue de la Roseraie, 1211 Geneva, Switzerland
3Division of Laboratory Medicine, Department of Genetics and Laboratory Medicine, Geneva University Hospitals, 4 Rue Gabrielle-Perret-Gentil, 1205 Geneva, Switzerland

Received 22 July 2013; Revised 18 December 2013; Accepted 19 December 2013; Published 4 February 2014

Academic Editor: Eric F. Morand

Copyright © 2014 Alessandra Puddu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Glucagon-like peptide-1 (GLP-1), an intestinal hormone contributing to glucose homeostasis, is synthesized by proglucagon and secreted from intestinal neuroendocrine cells in response to nutrients. GLP-1 secretion is impaired in type 2 diabetes patients. Here, we aimed at investigating whether diabetic toxic products (glycated serum (GS) or high levels of glucose (HG)) may affect viability, function, and insulin sensitivity of the GLP-1 secreting cell line GLUTag. Cells were cultured for 5 days in presence or absence of different dilutions of GS or HG. GS and HG (alone or in combination) increased reactive oxygen species (ROS) production and upregulated proglucagon mRNA expression as compared to control medium. Only HG increased total production and release of active GLP-1, while GS alone abrogated secretion of active GLP-1. HG-mediated effects were associated with the increased cell content of the prohormone convertase 1/3 (PC 1/3), while GS alone downregulated this enzyme. HG upregulated Glucokinase (GK) and downregulated SYNTHAXIN-1. GS abrogated SYNTHAXIN-1 and SNAP-25. Finally, high doses of GS alone or in combination with HG reduced insulin-mediated IRS-1 phosphorylation. In conclusion, we showed that GS and HG might regulate different pathways of GLP-1 production in diabetes, directly altering the function of neuroendocrine cells secreting this hormone.