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Glucagon-like peptide-1 triggers protective pathways in pancreatic beta-cells exposed to glycated serum

Puddu, Alessandra
Sanguineti, Roberta
Durante, Arianna
Nencioni, Alessio
Viviani, Giorgio L
Published in Mediators of inflammation. 2013, vol. 2013, 317120
Abstract Advanced glycation end products (AGEs) might play a pathophysiological role in the development of diabetes and its complications. AGEs negatively affect pancreatic beta-cell function and the expression of transcriptional factors regulating insulin gene. Glucagon-like peptide-1 (GLP-1), an incretin hormone that regulates glucose homeostasis, might counteract the harmful effects of AGEs on the beta cells in culture. The aim of this study was to identify the intracellular mechanisms underlying GLP-1-mediated protection from AGE-induced detrimental activities in pancreatic beta cells. HIT-T15 cells were cultured for 5 days with glycated serum (GS, consisting in a pool of AGEs), in the presence or absence of 10 nmol/L GLP-1. After evaluation of oxidative stress, we determined the expression and subcellular localization of proteins involved in maintaining redox balance and insulin gene expression, such as nuclear factor erythroid-derived 2 (Nrf2), glutathione reductase, PDX-1, and MafA. Then, we investigated proinsulin production. The results showed that GS increased oxidative stress, reduced protein expression of all investigated factors through proteasome activation, and decreased proinsulin content. Furthermore, GS reduced ability of PDX-1 and MafA to bind DNA. Coincubation with GLP-1 reversed these GS-mediated detrimental effects. In conclusion, GLP-1, protecting cells against oxidants, triggers protective intercellular pathways in HIT-T15 cells exposed to GS.
Keywords AnimalsCell LineCricetinaeGlucagon-Like Peptide 1/pharmacologyGlycosylation End Products, Advanced/pharmacologyHomeodomain Proteins/metabolismImmunoblottingInsulin-Secreting Cells/drug effects/metabolismProtein Binding/drug effectsReverse Transcriptase Polymerase Chain ReactionTrans-Activators/metabolism
PMID: 23737644
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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 triggers protective pathways in pancreatic beta-cells exposed to glycated serum. In: Mediators of inflammation, 2013, vol. 2013, p. 317120. doi: 10.1155/2013/317120 https://archive-ouverte.unige.ch/unige:77541

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Deposited on : 2015-11-23

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