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Retinal pigment epithelial cells express a functional receptor for glucagon-like peptide-1 (GLP-1)

Puddu, Alessandra
Sanguineti, Roberta
Viviani, Giorgio L
Published in Mediators of inflammation. 2013, vol. 2013, 975032
Abstract Glucagon-like peptide-1 (GLP-1) is a gut-derived incretin hormone that has been shown to improve glucose homeostasis in type 2 diabetes. The biological effects of GLP-1 are mediated by its specific receptor GLP-1R that is expressed in a wide range of tissues, where it is responsible of the extra-pancreatic effects of GLP-1. Since the retinal pigment epithelium (RPE), that forms the outer retinal barrier, has a key role in protecting from diabetic retinopathy (DR), we investigated the potential expression and function of GLP-1R in a RPE cell line. ARPE-19 cells were cultured in DMEM/F12 supplemented with 10% FBS. The expression of GLP-1R was evaluated at both mRNA and protein levels. Then, the activation postreceptor intracellular signal transduction pathways (extracellular signal-regulated kinases 1 and 2 [ERK1/2] and protein kinase B [PKB]) were assessed by western blot in normal cells or silenced for GLP-1R in the presence or absence of 10 nmol/L GLP-1. The potential connections between intracellular signalling pathways triggered by GLP-1 stimulation were performed before incubating cells with kinase pharmacological inhibitors of mitogen-activated protein kinase (MEK)1/2, phosphatydilinositol-3kinase (PI3K), or epidermal growth factor receptor (EGFR). The results showed that GLP1R is expressed at both mRNA and protein level in ARPE-19 cells. Stimulation with GLP-1 strongly activated PKB and ERK1/2 phosphorylation till 40 min of exposure. GLP-1-mediated activation of both kinases was dependent on the upstream activation of PI3K and EGFR. Finally, treatment with GLP-1 did not affect the spontaneous release of VEGF-A from ARPE-19 cells. In conclusion, this paper showed that the presence of functional GLP-1R is expressed in RPE cells. These data might represent the rationale to further investigate the potential direct beneficial effects of GLP-1 treatment against DR.
Keywords Cell LineCell SurvivalEnzyme Inhibitors/pharmacologyGene SilencingGlucagon-Like Peptide 1/pharmacologyHumansPhosphatidylinositol 3-Kinases/metabolismPhosphorylationProto-Oncogene Proteins c-akt/metabolismRNA InterferenceReceptor, Epidermal Growth Factor/metabolismReceptors, Glucagon/metabolismRetinal Pigment Epithelium/cytology/pathologyReverse Transcriptase Polymerase Chain ReactionSignal TransductionTime FactorsVascular Endothelial Growth Factor A/metabolism
PMID: 24307763
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Research group L'athérosclérose et ses complications cliniques (591)
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PUDDU, Alessandra et al. Retinal pigment epithelial cells express a functional receptor for glucagon-like peptide-1 (GLP-1). In: Mediators of inflammation, 2013, vol. 2013, p. 975032. doi: 10.1155/2013/975032 https://archive-ouverte.unige.ch/unige:77546

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Deposited on : 2015-11-23

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