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Title

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

Authors
Puddu, Alessandra
Sanguineti, Roberta
Viviani, Giorgio L
Published in Mediators of Inflammation. 2014, vol. 2014, p. 923120
Abstract 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.
Keywords Blood Glucose/metabolismCell LineCell SurvivalDown-RegulationGene Expression RegulationGlucagon-Like Peptide 1/bloodGlucokinase/metabolismHumansInflammation/bloodInsulin/metabolismProglucagon/metabolismRNA, Messenger/metabolismReactive Oxygen Species/metabolismSynaptosomal-Associated Protein 25/metabolismSyntaxin 1/metabolism
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PMID: 24648662
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Research group L'athérosclérose et ses complications cliniques (591)
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PUDDU, Alessandra et al. 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. In: Mediators of Inflammation, 2014, vol. 2014, p. 923120. https://archive-ouverte.unige.ch/unige:77554

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Deposited on : 2015-11-23

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