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

Mediators Inflamm. 2013;2013:975032. doi: 10.1155/2013/975032. Epub 2013 Nov 6.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Cell Survival
  • Enzyme Inhibitors / pharmacology
  • ErbB Receptors / metabolism
  • Gene Silencing
  • Glucagon-Like Peptide 1 / pharmacology*
  • Glucagon-Like Peptide-1 Receptor
  • Humans
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA Interference
  • Receptors, Glucagon / metabolism*
  • Retinal Pigment Epithelium / cytology*
  • Retinal Pigment Epithelium / pathology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • Time Factors
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Enzyme Inhibitors
  • GLP1R protein, human
  • Glucagon-Like Peptide-1 Receptor
  • Receptors, Glucagon
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Glucagon-Like Peptide 1
  • Phosphatidylinositol 3-Kinases
  • ErbB Receptors
  • Proto-Oncogene Proteins c-akt